Proposal #: 15-33

2013 FASEB SCIENCE RESEARCH CONFERENCES ADVISORY COMMITTEE MEETING

TOPIC FOR CONSIDERATION TOPIC NAME: MITOCHONDRIAL BIOGENESIS AND DYNAMICS IN HEALTH, DISEASE AND AGING PREVIOUS TITLE: Mitochondrial Biogenesis and Dynamics in Health, Disease and Aging SUBMITTED BY: Grazia Isaya, Mayo Clinic Liza Pon, Columbia University YEAR REQUESTED FOR

SCHEDULING: 2015

SITE REQUESTS: 1. Palm Beach, FL

2. Chicago, IL 3. Nassau, Bahamas

DATE REQUESTS: 1. May 3-8, 2015

2. May 10-15, 2015 3. May 17-22, 2015

YEAR(S) CONFERENCE

HAS BEEN HELD: 2007, 2009, 2011, 2013

NOTES: To the best of our knowledge, there is not a direct conflict with any other

FASEB SRC or other society or industry meeting.

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Section 1: Organizer Responsibilities:

By submitting a FASEB Summer Research Conference proposal for consideration by the FASEB SRC Advisory Committee, the organizer (s) accepts the responsibility for producing a successful conference. Such responsibilities include: 1. Anything related to the scientific portion of your conference. You will need to provide the conference title

and topics. The conference title and topics should be timely and attractive.

2. Attendance to your conference is expected to be no less than 100 participants.

3. All fund raising efforts are the responsibility of the organizers with support and guidance by the FASEB SRC Staff. FASEB will provide $10,000 for each conference to help defray a portion of travel and registration costs for speakers.

4. Contacting all speakers and session chairs to invite and confirm their participation. Speakers should be

informed that their expenses will be reimbursed after the conference and only to the extent that funds are available. We recommend you do not commitment to a speaker a specific amount of funds prior to the conference. (Note: Invited speakers and session chairs are required to remain at the conference for a minimum of three full days and three full nights in order to be eligible for reimbursement of any conference related expenses.)

5. Reviewing and approving the submitted attendee applications.

6. Including a “Meet the Expert” session in your program. This session is aimed at encouraging the younger investigators an opportunity to network with the more established and senior PIs in your field.

7. Providing a final conference program to your Conference Manager three weeks prior to the conference.

The program will include the speaker abstracts (in presentation order), poster abstracts, and a poster listing of the submitted abstracts. The Conference Manager will prepare the cover for the program, the participant list and have the final packet of materials reproduced and shipped to the venue.

8. Constant communication with your Conference Manager. By doing so, this will eliminate any

miscommunication or understanding of the policies and procedures that will needed to be followed.

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Section 2: Conference Title & Organizer Information

TITLE OF CONFERENCE: Mitochondrial Biogenesis and Dynamics in Health, Disease and Aging # of EXPECTED ATTENDEES: 100-110 Preferred Primary Point of Contact for Proposal Questions: Name: Grazia Isaya Full Address: Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA Telephone: 507-266-0110 Email Address: isaya@mayo.edu Science Categories (select up to 3) 1) Biochemistry 2) Cell Biology 3) Genetics Organizing Committee: Co-organizers: *Grazia Isaya, M.D., Ph.D., Professor Departments of Pediatric & Adolescent Medicine and Biochemistry & Molecular Biology, Mayo Clinic 200 First Street SW, Rochester, MN 55905, USA Phone: 507-266-0110 (office) Email: isaya@mayo.edu *Liza Pon, Ph.D., Professor Department of Pathology & Cell Biology and Institute for Human Nutrition, C o l u m b i a University 630 W. 168th Street, New York, NY 10032, USA Phone: 212-305-1947 (office) Email: lap5@columbia.edu *NIH Biosketch attached at the end of this document

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Section 3: Program Submission Requirements & Outline Overview of Program Flow # of Days: 5 (Sunday-Thursday) # of Sessions per day: 2 (Monday-Thursday) # of Speakers per day: 8 invited + 1-2 short talks selected from poster abstracts # of Session chairs per day: 2 # of Breakouts per day: 2 # of Abstracts per day: ~50 Posters and ~4 Short talks Day One (Sunday) Afternoon: Registration Evening: FASEB SRC Welcome Reception & Dinner Keynote Speaker: Jodi Nunnari, UC Davis, CA, USA (CS)(W)

Mitochondrial dynamics: Past, present and future Day Two (Monday) Session 1 (AM) Title: Biogenesis and Function of Mitochondrial Macromolecules Session Chair: Rosemary Stuart, Marquette University, WI, USA (C)(W) Speaker 1 Rosemary Stuart, Marquette University, WI, USA (CS)(W) Mapping the mitochondrial ribosomes Speaker 2 Toni Barrientos, University of Miami Health System, Miami FL (CS) The biogenetic pathway of mitochondrial ribosomes Speaker 3 Nikolaus Pfanner, University of Freiburg, Germany (CS) Import and assembly of mitochondrial proteins Speaker 4 Carla Koehler, University of California, Los Angeles (CS)(W) The machinery for translocation of redox-regulated proteins into mitochondria Number of short talks from posters: 1-2 Session 2 (PM) Title: Mitochondrial Protein Quality Control Session Chair: Thomas Langer, CECAD Cologne, Germany (C) Speaker 1 Thomas Langer, CECAD Cologne, Germany (CS) Proteolytic control of mitochondrial membrane dynamics and apoptosis Speaker 2 Carolyn Suzuki, New Jersey Medical School, Newark NJ, USA (CS)(W)(N) Mitochondrial AAA+ Lon protease in protein quality control and mtDNA dynamic Speaker 3 Ed Fon, McGill University, Montreal, Canada (CS)(N) Function of Parkin and PINK1 in mitochondrial quality-control Speaker 4 Luke Wiseman, Scripps Research Institute, La Jolla CA, USA (CS)(N) Adapting mitochondrial proteostasis capacity through stress-responsive signaling Number of short talks from posters: 1-2

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Day Three (Tuesday) Session 3 (AM) Title: Heme, Fe-S clusters and Metal Cofactors in Mitochondrial Metabolism Session Chair: Dennis Winge, University of Utah, UT, USA (C) Speaker 1 Dennis Winge, University of Utah, UT, USA (CS) Assembly of Succinate Dehydrogenase: Interplay between iron-sulfur cofactor insertion and subunit assembly Speaker 2 Roland Lill, Philipps Universität, Marburg, Germany (CS) Mitochondrial iron-sulfur protein biogenesis: Mechanisms and diseases Speaker 3 Tania Baker, M.I.T. Cambridge, MA, USA (W)(N) The role of the ClpX chaperone in heme biosynthesis Speaker 4 Scot Leary, University of Saskatchewan, Canada (CS)(NEW) A mitochondrial signaling pathway that controls cellular copper levels Number of short talks from posters: 1-2 Session 4 (PM) Mitochondrial stress in cell signaling and aging Session Chair: Luke Szweda, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA (C) Speaker 1 Luke Szweda, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA (CS)(N) Cardiac Mitochondria: Nutrient Sensors for Redox-Driven Metabolic Reprogramming Speaker 2 Dan Gottschling, Fred Hutchinson Cancer Research Center, Seattle, WA, USA (CS)(N) Organelle deterioration with age: The limits of an interconnected cellular system Speaker 3 Gerry Shadel, Yale University, New Haven CT, USA (CS) Mitochondrial stress signaling in disease and aging Speaker 4 Jared Rutter, University of Utah, Salt Lake City UT, USA (CS) Stress regulation of mitochondrial quality control Number of short talks from posters: 1-2 Day Four (Wednesday) Session 5 (AM) Mitochondrial dynamics in development and disease Session Chair: Jodi Nunnari, UC Davis, CA, USA (C)(W) Speaker 1 Zu-Hang Sheng, NIH/NINDS, Bethesda MA, USA (CS)(N) Regulation of axonal mitochondrial transport: impact on synaptic function and neurodegeneration Speaker 2 Mike Ryan, La Trobe University, Melbourne, Australia (CS)(N) Structural and functional analysis of dynamin adaptors required for mitochondrial fission Speaker 3 Henry Higgs, Dartmouth Medical School, Hanover NH, USA (CS)(N) Role of actin, formins, and myosin in mitochondrial fission at the ER interface Speaker 4 Alex van der Bliek, UCLA, Los Angeles CA, USA (CS)(N) Stress induced control of mitochondrial fission and fusion Number of short talks from posters: 1-2

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Session 6 (PM) Nuclear DNA-driven mechanisms of mitochondrial disease Session Chair: Massimo Zeviani, MRC Cambridge, UK (C)(N) Speaker 1 Massimo Zeviani, MRC Cambridge, UK (CS)(N) Unconventional disease genes and mechanisms of mitochondrial dysfunction Speaker 2 Eric Shoubridge, McGill University, Montreal, Canada (CS)

Posttranscriptional regulation of mitochondrial gene expression in health and disease

Speaker 3 Helene Puccio, IGBMC, Strasbourg, France (CS)(W)(N) Cellular and animal models of nuclear-driven mitochondrial neurodegenerative disease Speaker 4 Gloria Ferreira, University of South Florida, Tampa FL, USA (CS)(W)(N) Orchestration between mitochondrial iron trafficking and porphyrin synthesis Number of short talks from posters: 1-2 Day Five (Thursday) Session 7 (AM) New Pathways, Biomarkers and Technologies to Study Mitochondrial Function Session Chair: Carlos Moraes, University of Miami, FL, USA (C)(M) Speaker 1 Carlos Moraes, University of Miami, FL, USA (CS)(M) The use of mitoTALENs to manipulate mtDNA hetereoplasmy Speaker 2 Uday B. Kompella, University of Colorado Denver, Aurora CO, USA (CS)(N) Nanotechnology and drug design strategies for mitochondrial delivery Speaker 3 Giovanni Manfredi, Weill Cornell Medical College, New York, NY, USA (CS) The role of soluble adenylyl cyclase in the regulation of mitochondrial energy metabolism Speaker 4 Daniel Peeper, Netherlands Cancer Institute, Amsterdam, The Netherlands (CS)(N) Cell senescence, metabolism and cancer Number of short talks from posters: 1-2 Meet the Expert Session Session 8 (PM) Challenges and Opportunities in Mitochondrial Biology and Medicine Session Chair: Enrique Cadenas, USC School of Pharmacy, Los Angeles, CA, USA (C)(M)(N) Speaker 1 Paul S. Brookes, University of Rochester Medical Center, Rochester NY, USA (CS)(N)

Mitochondria as drug targets in ischemic heart disease and cardiomyopathy Speaker 2 Eugenia Trushina, Mayo Clinic, Rochester MN, USA (CS)(W)(N)

Mitochondrial dynamics and function in progression of Alzheimer's Disease Speaker 3 Eric Schon, Columbia University, New York, NY, USA (CS)(N)

Mitochondrial-associated ER membranes in Alzheimer’s Disease Speaker 4 Enrique Cadenas, USC School of Pharmacy, Los Angeles, CA, USA (CS)(M)(N)

The energy-redox axis as a therapeutic target in brain aging and neurodegeneration Number of short talks from posters: 1-2

End of Conference ***ALL TALK TITLES LISTED ARE TENTATIVE***

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Section 4: Content Assessment Number of session chairs that have confirmed participation: 8 (all) Number of women included within the entire program: 10 ( including the 2 organizers) Number of session chairs/speakers of a minority group: 2 Number of “new” speakers to the Conference: 21 Number of confirmed speakers: 31/32 Number of talks set aside for junior-level investigators: 8-16 Number of poster sessions: 3 Brief Description of how poster sessions will be organized:

They will be organized differently than at the 2013 Conference based on the Course Evaluations Drs. Shadel and Manfredi have kindly shared with us. All posters will be up for the entire duration of the Conference. I n t he first session, Authors of odd numbered posters will be required to be at their posters; in the second session, Authors of even numbered posters will be required to attend; the third session will be open to all Authors to present. However, all Authors will be encouraged to be present at each of the three sessions. These changes should give time to all attendees to see the posters they are most interested in with the presenters in attendance.

Potential Conflicts with other FASEB, society, or industry meetings:

The annual UMDF “Mitochondrial Medicine” Meeting is usually held in June. The main focus of this meeting is on mitochondrial disease and treatments thereof, which would only cover a fraction of the attendees our Conference typically attracts, i.e. basic scientists in the areas of Biochemistry, Cell Biology and Genetics.

The Bioenergetics Gordon Conference is scheduled fo r 2015, but dates are not known currently. The main focus of this meeting only partially overlaps the broad spectrum of topics to be addressed by our Conference.

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Section 5: Scheduling & Location Preferences Preferred dates:

Week 1: May 3-8 (Sun-Thur) Week 2: May 10-15 (Sun-Thur) Week 3: May 17-22 (Su-Thur) Preferred type of facility: Conference Center

Preferred locations:

1. Palm Beach FL 2. Chicago IL 3. Nassau Bahamas

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Section 6: Justification

1. Explain why this topic is of high current interest to the scientific community.

It is increasingly clear that mitochondria play many critical functional roles in all eukaryotic cells including

energy production, heme synthesis, Fe-S cluster assembly, iron and copper homeostasis, and reactive

oxygen species (ROS) production. The macromolecular machines responsible for carrying out these

critical functions continue to attract intense interest across disciplines with rapidly advancing studies at

the animal, cellular, biochemical and structural levels.

Simultaneously, it is increasingly apparent that the maintenance of functional mitochondria is a complex

task that requires integration of such processes as (1) the biogenesis of both nuclear-DNA and

mitochondrial-DNA encoded proteins, (2) quality control and turnover of all of these proteins, and (3)

mitochondrial dynamics. These are also very active areas of basic research across different fundamental

disciplines.

Not surprisingly, mitochondria are increasingly implicated in a variety of pathophysiological mechanisms

underlying such disorders as inborn errors of metabolism, neurodegenerative disease, cardiovascular

disease, cancer, and unhealthy aging, which are subjects of intense biomedical research.

Much active research also aims to the identification of new signaling pathways involved in mitochondrial

regulation as well as novel biomarkers and innovative technologies to monitor and manipulate

mitochondrial function with an eye to potential medical applications.

Given the fast pace at which all of the areas discussed above are advancing, disseminating and integrating

this large body of information is critically needed. Indeed, this Conference will be of interest to a broad

range of investigators from multiple fields (cell biology, molecular biology, genetics, biochemistry,

bioenergetics, physiology, pathology, nanotechnology, and medicine), and will provide a highly

interdisciplinary learning experience for all participants. The two previous meetings held in 2011 and 2012

were all well attended and extremely well received.

2. Is this a rapidly growing field?

As discussed above, this is a rapidly growing field because mitochondria play many critical functional

roles in the cell. As such, mitochondria are implicated in a constantly broadening spectrum of

pathophysiological mechanisms that are the subject of intense studies across different, although

interdependent, disciplines including cell biology, molecular biology, genetics, biochemistry,

bioenergetics, physiology, pathology, nanotechnology, and medicine. In particular, the elucidation of

unexpected roles of mitochondria in human disease and age-related pathology is occurring at an

unprecedented rate. This includes involvement in highly prevalent conditions such as cancer,

cardiovascular and neurodegenerative disease among others. Consequently there is an urgent need for

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new biomarkers and technologies to study and possibly manipulate mitochondrial function. There are also

emerging new challenges as well as therapeutic opportunities. This Conference will have sessions that

highlight these “new frontiers” in mitochondrial research.

3. Have there been previous conferences of this topic? If so, where and when were the conferences held? How

many participants attended? (Additionally, consider whether or not another similar conference/meeting is scheduled

that might cause a conflict).

Recent meetings on this topic:

The Gordon Conferences on Mitochondria and Chloroplasts (July 2014, Lucca, Italy), Iron-Sulfur Enzymes

(June 2014, Easton, MA), and Oxygen Radicals (February 2014, Ventura Beach, CA)

These meetings are only partially focused on mitochondria and will take place one year before our Conference.

Euromit 2014 (June 2011, Tampere, Finland)

This meeting is dedicated to understanding how mitochondria are involved in disease and will take place one year

before our Conference.

Potential conflicts:

The annual UMDF “Mitochondrial Medicine” Meeting is usually held in June. The main focus of this meeting

is on mitochondrial disease and treatments thereof, which would only cover a fraction of the attendees our

Conference typically attracts, i.e. basic scientists in the areas of Biochemistry, Cell Biology and Genetics.

The Bioenergetics Gordon Conference is scheduled for 2015, but dates are not known currently. The main

focus of this meeting only partially overlaps the broad spectrum of topics to be addressed by our Conference.

4. How many participants do you expect to attend the conference?

At the Conferences in 2009, 2011 and 2013 there were 100, 101, and 108 attendees, respectively. Therefore,

we estimate 100-110 attendees at the 2015 meeting. Holding the conference in the spring is expected to

increase the number of participants from Europe and may result in even higher numbers.

5. What is the percentage of women have participated in this Conference in the past (if it has been previously

held)?

35-40%

6. How will you recruit young investigators to attend and participate in the Conference?

We have already listed four junior-level investigators (NEW) in the tentative program, all of whom have

agreed to give a talk at the meeting. These individuals were suggested by confirmed session chairs.

Additional young investigators will be recruited by e-mail and by advertising at other mitochondrial

meetings. We have large email lists from previous mitochondrial meetings and can advertise the meeting

through this mechanism. Finally, additional junior investigators will be selected from submitted abstracts

to present short platform talks. We expect a total of 8-10 presentations (at least 1 per session) from junior-

level investigators.

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7. How will you recruit and select new speakers?

Our preliminary program already contains 21 new speakers to the Conference that were identified by

querying the confirmed session chairs in this regard.

8. From what sources and resources will you use to solicit funds for the conference? (Provide specifics).

NIGMS, NIH, United Mitochondrial Disease Foundation, American Heart Association, Muscular Dystrophy

Association, EMBO and FEBS, Army Research Office, Bach Pharma, Nikon, Zeiss, Seahorse Bioscience,

Ellison Medical Foundation, and the publishers of journals including Cell, Nature, Science, Journal of Cell

Biology, Journal of Cell Science, Molecular Biology of the Cell, and Mitochondrion.

9. Who will attend the Conference? (Provide specifics).

Scientists and physician-scientists members of the following societies: American Society of Cell Biology,

ASBMB, ASIP, AFAR, EMBO and disciplines of Cell Biology, Molecular Biology, Biochemistry, and

Structural Biology as well as those studying mechanisms of mitochondrial diseases. Because the relevant

role of mitochondrial function in stroke, cardiovascular function and neurodegenerative disease, among

other conditions, we anticipate to attract researchers in the Friedreich’s Ataxia Research Alliance and the

American Heart Association.

10. Where will you advertise the conference? What types of media will you use to advertise your conference?

(Provide specifics).

E-mails to previous attendees and from attendees of other mitochondrial meetings (EuroMit, GRC on

chloroplasts and mitochondria, UMDF annual meeting), advertisements at the EuroMit meeting and the

GRC on chloroplasts and mitochondria, as well as FASEB sponsored advertisements for the FASEB

meeting series. There is also a large mitochondrial interest group e-mail list organized by Steve Zullo at

NIH, and we will advertise the meeting here as well.

11. Are you planning on submitting a similar application to another organization for additional funding and

sponsorship? If yes, please clarify.

No.

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BIOGRAPHICAL SKETCH

NAME

Grazia Isaya, M.D., Ph.D. POSITION TITLE

Professor of Pediatrics Professor of Biochemistry and Molecular Biology

eRA COMMONS USER NAME

ISAYA1

EDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, such as nursing, and include postdoctoral training.)

INSTITUTION AND LOCATION DEGREE (if applicable)

YEAR(s) FIELD OF STUDY

University of Padova, Padova, Italy M.D. 1982 Medicine

University of Padova, Padova, Italy Residency 1986 Neurology

University of Padova, Padova, Italy Ph.D. 1991 Developmental Sciences

A. PERSONAL STATEMENT My commitment to mitochondrial research goes back 30 years. During my M.D. and Neurology training I worked in the laboratory of Corrado Angelini, at Padova University, focusing on the biochemical bases of mitochondrial myopathies. During my Ph.D. training I worked in the laboratory of Leon Rosenberg, at Yale University, and became interested in mitochondrial processing peptidases required for the maturation of nucleus-encoded subunits of the respiratory chain. In 1994 I started my independent research program at Yale and then at Mayo Clinic, centering on the mechanisms required for the maintenance of oxidative phosphorylation and the protection from oxidative stress. A major turning point was in 1996, when we isolated yeast frataxin from a genetic screening designed to identify nuclear genes involved in the maintenance of mtDNA integrity. At that time, human frataxin had just been linked to the neuro-degenerative disease Friedreich ataxia. Like many other labs, we became very interested in elucidating the function of frataxin, which was completely unknown. We were the first to show that frataxin is an iron-binding protein, and we have since contributed to the biochemical and structural understanding of this critical molecule, as well as its role in the biogenesis of mitochondrial Fe-S clusters.

These research experiences and contributions have prepared me to serve as Co-organizer of the FASEB Conference on Mitochondrial Biogenesis Dynamics in Health, Disease and Aging. I also bring extensive experience in mitochondrial basic and translational research peer-review having served as regular member of the NIH/NIA Cellular Mechanisms of Aging and Development (CMAD) study section, and currently serving as member of the Friedreich Ataxia Research Alliance Scientific Advisory Committee and the Muscular Dystrophy Association Medical Advisory Committee. I am excited to serve as Conference Co-organizer with Dr. Liza Pon. She and I share a strong interest in mitochondrial research. Our complementary experiences and qualifications are ideal for our leading roles in this Conference. B. POSITIONS AND SERVICE 1981-82 Intern, University of Padova School of Medicine, Dept. of Neurology, Padova, Italy 1982-86 Resident, University of Padova School of Medicine, Dept. of Neurology, Padova, Italy 1987-89 Postdoctoral Associate, Yale University School of Medicine, Dept. of Genetics 1989-94 Associate Res. Sci., Yale University School of Medicine, Dept. of Genetics 1994-98 Assistant Professor, Yale University School of Medicine, Dept. of Genetics 1998-03 Senior Associate Consultant, Department of Pediatric & Adolescent Medicine, Mayo Clinic,

Rochester, MN 1998- Associate Professor of Pediatrics, Mayo Medical School, Rochester, MN

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2003- Consultant, Departments of Pediatric & Adolescent Medicine and Biochemistry & Molecular Biology, Mayo Clinic, Rochester, MN

2006- Professor of Pediatrics, Mayo Clinic, College of Medicine 2006- Professor of Biochemistry and Molecular Biology, Mayo Clinic, College of Medicine 2007- Director, Mayo Medical Scientist Training Program 2011- Research Chair, Pediatric and Adolescent Medicine and Mayo Clinic Children Center Professional Memberships and Service

1982-Present: Italian Medical License; 1983-Present: Italian Medical Association; 1986-Present: Italian Board of Neurology; 1994-Present: American Society of Microbiology; 1999-Present: American Society of Human Genetics; 2002-Present: American Society for Biochemistry and Molecular Biology; 2005-Present: International BioIron Society; 2003-06: Telethon-Italia Advisory Committee; 2006-2010: NIH/NIA Cellular Mechanisms of Aging and Development (CMAD) study section, regular member; 2007-Present: Friedreich Ataxia Research Alliance Scientific Advisory Committee; 1999-2010; 2013-present: Muscular Dystrophy Association Medical Advisory Committee; 2013-present: Mitochondrion Editorial Board C. SELECTED PUBLICATIONS (from 62 total) 1. Isaya G, Kalousek F, Rosenberg LE. Sequence analysis of rat mitochondrial intermediate peptidase:

similarity to zinc metallopeptidases and to a putative yeast homologue. Proc. Natl. Acad. Sci. USA 89:8317-8321, 1992.

2. Adamec J, Rusnak F, Owen WG, Naylor S, Benson LM, Isaya G. Iron-dependent self-assembly of recombinant yeast frataxin: Implications for Friedreich ataxia. Am. J. Hum. Genet. 67:549-562, 2000.

3. Cavadini P, Gellera C, Patel PI, Isaya G. Human frataxin maintains mitochondrial iron homeostasis in Saccharomyces cerevisiae. Hum. Mol. Genet. 9:2523-2530, 2000.

4. Cavadini P, Adamec J, Taroni F, Gakh O, Isaya G. Two-step processing of human frataxin by mitochondrial processing peptidase: Precursor and intermediate forms are cleaved at different rates. J. Biol. Chem. 275:41469-41475, 2000.

5. Cavadini P, O’Neill HA, Benada O, Isaya G. Assembly and iron binding properties of human frataxin, the protein deficient in Friedreich ataxia. Hum. Mol. Genet. 11:217-227, 2002.

6. Park S, Gakh O, Mooney SM, Isaya G. The ferroxidase activity of yeast frataxin. J. Biol. Chem. 277:38589-38595, 2002.

7. Bulteau AL, O'Neill HA, Kennedy MC, Ikeda-Saito M, Isaya G, Szweda LI. Frataxin acts as an iron chaperone protein to modulate mitochondrial aconitase activity. Science 305:242-245, 2004.

8. O’Neill HA, Gakh O, Isaya G. Supramolecular assemblies of human frataxin are formed via subunit-subunit interactions mediated by a non-conserved amino-terminal region. J. Mol. Biol. 345:433-439, 2005.

9. Gakh O, Park S, Liu G, Macomber L, Imlay JA, Ferreira GC, Isaya G. Mitochondrial iron detoxification is a primary function of frataxin that limits oxidative damage and preserves cell longevity. Hum Mol Genet. 15(3):467-479, 2006.

10. Karlberg T, Schagerlöf U, Gakh O, Park S, Ryde U, Lindahl M, Leath K, Garman E, Isaya G*, Al-Karadaghi S*. The structures of frataxin oligomers reveal the mechanism for the delivery and detoxification of iron. Structure 14:1535-1546, 2006. *Co-senior authors

11. Babady NE, Pang YP, Elpeleg O, Isaya G. Cryptic proteolytic activity of dihydrolipoamide dehydrogenase. Proc Natl Acad Sci U S A 104:6158-6163, 2007.

12. Gakh O, Smith DY, Isaya G. Assembly of the iron-binding protein frataxin in S. cerevisiae responds to dynamic changes in mitochondrial iron influx and stress level. J Biol Chem 283:31500-31510, 2008. PMCID: PMC2581586.

13. Schagerlöf U, Elmlund H, Gakh O, Nordlund G, Hebert H, Lindahl M, Isaya G*, Al-Karadaghi S*. Structural basis of the iron storage function of frataxin from single-particle reconstruction of the iron-loaded oligomer. Biochemistry 47:4948-4954, 2008. *Co-senior authors

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14. Li H, Gakh O, Smith DY 4th, Isaya G. Oligomeric yeast frataxin drives assembly of core machinery for mitochondrial iron-sulfur cluster synthesis. J Biol Chem 284:21971-21980, 2009. PMCID: PMC2755921.

15. Gakh O, Bedekovics T, Duncan SF, Smith DY 4th, Berkholz DS, Isaya G. Normal and Friedreich ataxia cells express different isoforms of frataxin with complementary roles in iron-sulfur cluster assembly. J Biol Chem, 2010 Dec 3; 285(49):38486-501. PMID: 20889668.

16. Bedekovics T, Li H, Gajdos GB, Isaya G. Leucine biosynthesis regulates cytoplasmic iron-sulfur enzyme biogenesis in an Atm1-independent manner. J Biol Chem 2011 Nov 25; 286(47):40878-88. PMID: 21926174.

17. Vaubel RA, Rustin P, Isaya G. Mutations in the dimer interface of dihydrolipoamide dehydrogenase promote site-specific oxidative damages in yeast and human cells. J Biol Chem 2011 Nov 18:286(46):40232-45. PMID: 21930696.

18. Bedekovics T, Li H, Gajdos GB, Isaya G. Leucine biosynthesis regulates cytoplasmic iron-sulfur enzyme biogenesis in an Atm1-independent manner. J Biol Chem 286:40878-40888, 2011. PMID: 21926174.

19. Vaubel RA, Rustin P, Isaya G. Mutations in the dimer interface of dihydrolipoamide dehydrogenase promote site-specific oxidative damages in yeast and human cells. J Biol Chem 286:40232-40245, 2011. PMID: 21930696.

20. Soderberg CA, Shkumatov AV, Rajan S, Gakh O, Svergun DI, Isaya G, Al-Karadaghi S. Oligomerization propensity and flexibility of yeast frataxin studied by X-ray crystallography and small-angle X-ray scattering. J Mol Biol. 2011 Dec 16;414(5):783-97. PMID: 22051511.

21. Vaubel RA, Isaya G. Iron-sulfur cluster synthesis, iron homeostasis and oxidative stress in Friedreich ataxia. Mol Cell Neurosci. 2013 Jul; 55:50-61. PMID: 22917739.

22. Li H, Gakh O, Smith DY 4th, Ranatunga WK, Isaya G. Missense Mutations Linked to Friedreich Ataxia Have Different but Synergistic Effects on Mitochondrial Frataxin Isoforms. J Biol Chem. 2013 Feb 8; 288(6):4116-27. PMID: 23269675.

23. Soderberg CA, Rajan, Shkumatov AV, Gakh O, Schaefer S, Ahlgren EC, Svergun DI, Isaya G, AL-Karadaghi S. J Biol Chem. 2013 Mar 22;288(12):8156-67. PMID: 23344952.

24. Ogllesbee D, Kroll C, Gakh O, Deutsch EC, Lynch DR, Gavrilova R, Tortorelli S, Raymond K, Gavrilov D, Rinaldo P, Matern D, Isaya G. High-throughput immunoassay for the biochemical diagnosis of Friedreich ataxia in dried blood spots and whole blood. Clin Chem. 2013 Jul 9 (Epub ahead of print). PMID: 23838345.

D. RESEARCH SUPPORT Active NIH/NIA 1RO1-AG015709-17 5/1/2011-4/31/2016 Co-PIs: G. Isaya (20%) and J. Thompson (10%) Title: New determinants of mtDNA integrity in yeast and heart The main goal is to elucidate the structural architecture and the catalytic mechanisms of the mitochondrial machinery responsible for the synthesis of iron-sulfur clusters NIH/NIGMS T32 GM 65841 7/2003-6/2018 PD: G. Isaya (no salary support) Title: Medical Scientist Training Program at Mayo Clinic The main goal is to train future generations of outstanding physician-scientists Sanford Pediatric Research Collaborative Award 7/1/2013-6/30/2014 Co-PIs: G. Isaya (2%) and P. Vitiello (2%) Title: Mechanisms of oxidative injury in Friedreich ataxia patients The main goal is to characterize novel interactions between human frataxin and mitochondrial oxido-reductases

BIOGRAPHICAL SKETCH Provide the following information for the key personnel and other significant contributors.

Follow this format for each person. DO NOT EXCEED FOUR PAGES.

NAME

Liza A. Pon, Ph.D POSITION TITLE Professor eRA COMMONS USER NAME

Ponliza EDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, such as nursing, and include postdoctoral training.)

INSTITUTION AND LOCATION DEGREE (if applicable) YEAR(s) FIELD OF STUDY

University of California, Berkeley, CA B.A. 1981 Biochemistry Tufts University Health Sciences, Boston, MA Ph.D. 1986 Biochemistry Biocenter, University of Basel, Switzerland Post-doc 1987-90 Biochemistry/Cell

Biology

A. Personal Statement

As a PhD student, I identified the protein now known as Steroidogenic acute regulatory proteins (StAR), a regulator of the rate-limiting step in steroid biosynthesis, which occurs in the inner mitochondrial membrane. As a post-doctoral trainee in the laboratory of Gottfried (Jeff) Schatz, I identified a role for contact sites between mitochondrial outer and inner membranes and import machinery in the inner mitochondrial membrane in mitochondrial protein import. In my own laboratory, we have taken a leading role in studying mitochondrial dynamics and inheritance in budding yeast. We obtained that first evidence that mitochondria undergo actin-dependent movement to and anchorage at the bud tip. We identified the conserved mechanisms underlying mitochondrial movement and identified conserved molecules that are required for anchorage of mitochondria in the bud tip. We also obtained the first evidence that mitochondria within a single cell are functionally distinct and that the fittest mitochondria, which have lower ROS and greater redox potential, are preferentially inherited by yeast daughter cells. Finally, we found that segregation of fitter from less fit mitochondria contributes to cellular fitness and lifespan.

I am qualified to serve as co-director of the FASEB meeting on Mitochondrial Biogenesis Dynamics in Health, Disease and Aging in part because I have a long-standing interest in mitochondria and have made significant contributions to the field. I am also deeply committed to the field. Indeed, I edited two volumes of Methods in Cell Biology on Mitochondria. These volumes bring together “classic” and new methods that enable new and experienced investigators to study mitochondria using biochemical, morphological or genetic approaches. Finally, I have co-chaired and chaired a Gordon Conference and therefore have experience as a meeting organizer. B. Positions and Honors. Professional Experience 1980–81 Undergraduate Research Assistant. Research Interest: Analysis of the role of the C-terminal

region of insulin on receptor binding and lipid metabolism using semi-synthetic insulin analogs. Advisor: Frederick H. Carpenter, Ph.D., Dept. of Biochemistry, University of California, Berkeley, CA.

1982–87 Graduate Research Assistant. Research Interest: Role of a regulatory phosphoprotein in cAMP-stimulated steroid hormone biosynthesis in the adrenal, corpus luteum, and testis. Advisor: Nanette Roberts Orme-Johnson, Ph.D., Dept. of Biochemistry, Tufts University, Boston, MA.

1987–90 NRSA Post-doctoral Fellow. Research Interest: Transport of proteins into mitochondria. Advisor: Gottfried Schatz, Ph.D., Dept. of Biochemistry, Biocenter, University of Basel, Basel, Switzerland.

1990–98 Assistant Professor, Department of Anatomy and Cell Biology, College of Physicians and Surgeons, Columbia University, New York, NY.

1990– Faculty of the Graduate School of Arts and Sciences, Columbia University in the City of New York.

1997– Director of the Optical Imaging facility for the Herbert Irving Comprehensive Cancer Center, College of Physicians and Surgeons, Columbia University.

1998–07 Associate Professor, Department of Anatomy and Cell Biology, College of Physicians and Surgeons, Columbia University.

2007- Professor, Department of Pathology and Cell Biology, College of Physicians and Surgeons, Columbia University.

2012- Professor, Institute for Human Nutrition, Columbia University. Professional activities/awards: 1998– ad hoc Reviewer for Shared Instrumentation Grants (NIH, 7/96); Special Study Section X-84

(NIH, 10/97); Cell Cytology and Physiology (CBY-1, NIHGMS, 2/99); Research Centers in Minority Institution (RCMI, 12/00); General Medicine program projects (NIH, 2/02 and 10/02); National Science Foundation (4/04); Shared Instrumentation Grants (NIH, ZRG1 CB-G (6/09); Shared Instrumentation Grants (NIH, ZRG1 CB-Q (11/09).

2000–01 Editor, Methods in Cell Biology 2000 Co-Chair for the Gordon Research Conference, “Plant and Fungal Cytoskeleton”, Andover, NH. 2002 Chair, Gordon Research Conference, “Plant and Fungal Cytoskeleton”, Andover, NH. 2000–04 Study Section Member, for Cell Development and Function-4 (CDF-4) NIH/NIGMS 2000–05 Editorial Board of Cell Motility and the Cytoskeleton 2006-07 Editor, Methods in Cell Biology 2006-11 Review Committee Member, Biomedical Research and Training (BRT-A) review committee,

NIH/NIGMS 2010-11 Chair, Biomedical Research and Training (BRT-A) Review Committee, NIH/NIGMS 2008- Editorial Board of the International Journal of Cell Biology. C. Peer-reviewed publications (selected from >65 publications). Most relevant publications 1. Mitochondria, 2nd Edition. Methods in Cell Biology volume 80 (2007) L.A. Pon and E.A Schon, editors.

Academic Press, Elsevier Inc, San Diego CA. The book is a widely used as a resource for methods and approaches to 1) isolate and subfractionate

mitochondria, 2) assay a variety of biochemical activities in mitochondria including respiration, ATP production, central metabolic acitivity, calcium regulation, and oxidative stress in vivo and in vitro, and 3) study mitochondrial genes, gene expression, protein import and dynamics. Optical microscopy methods including immunohistochemistry methods to visaulize mitochondria and measure mitochondrial respiratory activity, immunofluorescence methods to visualize mitochondria and proteins that localize to the organelle, targeted fluorescent methods to visualize miotchondria in living cells and fluorescent biosensors for detecting mitochondrial function in living cells are well respresented in the book, including chapters written by the Pon laboratory. The first edition of this Methods in Cell Biology volume, which was also edited by L. Pon and E. Schon, was published in 2001.

2. McFaline-Figueroa*, J.R., Vevea*, J.D., Swayne, T.C, Zhou, C., Liu, C., Boldogh, I.R, and Pon, L.A. (2011)

Mitochondrial quality control during inheritance affects lifespan and mother-daughter age asymmetry in budding yeast. Aging Cell 10:885-895. * There authors contributed equally to the manuscript. This paper provides the first documentation that 1) there is heterogeneity in mitochondrial ROS within individual yeast cells, 2) mitochondria with low ROS are preferentially inherited by daughter cells, and 3) defects in inheritance of fitter mitochondria by daughter cells compromises replicative lifespan and mother-daughter age asymmetry.

3. Swayne*, T.C., Zhou*, C., Boldogh*, I.R., Charalel, J.K., Mc-Faline-Figueroa, J.R., Thoms, S., Yang, C.,

Leung, G., McInnes, J, Erdmann, R., and Pon, L.A. (2011) Role for cER and Mmr1p in anchorage of mitochondria at sites of polarized surface growth in budding yeast. Curr. Biol. 21:1994-1999. * There authors contributed equally to the manuscript. Mitochondria are achored at sites of polarized growth including the bud tip of yeast, and the immunological and neuronal synapse. This manuscript provides the first evidence that mitochondria are anchored on ER underlying the plasma membrane in yeast, and for a direct role for a conserved member of a family of tethering proteins in this process. This paper was highlighted in a “Rapid Dispatch” in Curr. Biol. 21:R949-951.

4. Crider DG, García-Rodríguez LJ, Srivastava P, Peraza-Reyes L, Upadhyaya K, Boldogh IR, and Pon LA.

(2012) Rad53 is essential for a mitochondrial DNA inheritance checkpoint regulating G1 to S progression. J Cell Biol. 198(5):793-8.

This was the first evidence for a checkpoint that regulates cell cycle progression in response to loss of mitochondrial DNA. It was featured in “In this Issue” in the J. of Cell Biol.

5. Vevea JD, Swayne TC, Boldogh IR, and Pon LA. (2013) Inheritance of the fittest mitochondria in yeast.

Trends Cell Biol. (Epub ahead of print) This article is a Featured Review in the journal. Additional publications of importance to the field 1. García-Rodríguez L.J., Crider, D.G., Gay, A.C., Salanueva, I.J., Boldogh, I.R., Pon, L.A. (2009)

Mitochondrial inheritance is required for MEN-regulated cytokinesis in budding yeast. Curr Biol. 19:1730-5. PMID: 19818621.

2. Garcia-Rodriguez, L.J., Gay, A.C., and Pon, L.A. (2007) Puf3p is a mitochondrial protein that regulates mitochondrial biogenesis and inheritance, J. Cell Biol., 76:197-207. PMID: 17210948. This paper was featured in “In this Issue” in the Journal of Cell Biology.

3. Huckaba, T.M., Lipton, T., and Pon, L.A. (2006) Roles of type II myosin and a tropomyosin isoform in retrograde actin flow in budding yeast, J. Cell Biol.,175:957-69. PMID: 17178912. This was the topic of a “Rapid Dispatch” in Curr. Biol. 17:R244-7.

4. Huckaba, T.M., Gay, A.C., Pantalena, L.F., Yang, H-C., and Pon, L.A. (2004). Live cell imaging of the assembly, disassembly, and actin cable-dependent movement of endosomes and actin patches in the budding yeast, Saccharomyces cerevisiae. J. Cell Biol. 167:519-30. PMID: 15534003.

5. Boldogh, I.R., Ramcharan, S., and Pon, L.A. (2004). A type V myosin (Myo2p) and a Rab-like G-protein (Ypt11p) are required for retention of newly inherited mitochondria in yeast cells during cell division. Mol. Biol. Cell. 15:3994-4002. PMID: 1521531.

6. Yang, H-C., and Pon, L.A. (2002). Actin cable dynamics in budding yeast. Proc Natl Acad Sci, USA. 99:751-756. PMID: 11805329. Here, we visualized actin cable dynamics in living yeast for the first time, and found that actin cables are dynamic structures that undergo retrograde flow (elongation from their site of assembly in the bud, into the mother cell). It was selected for the plenary talk and cover for the abstract book for the meeting on “Yeast Cell Biology” at Cold Spring Harbor Laboratories in 2001.

7. Boldogh, I., Nowakowski, W.D., Yang, H-C., Karmon, S.L., Hayes, L., Yates, J., and Pon, L.A (2001). The Arp2/3 complex is required for actin-based mitochondrial motility in yeast. Proc Natl Acad Sci, USA. 98:3162-3167. PMID: 11248049. This study revealed the mechanism for bud-directed movement of mitochondria using actin cables as tracks. This work was featured in a “Meeting Highlights” in Science.

8. Yang, H-C., Palazzo, A., Swayne, T.C., and Pon, L.A. (1999). A retention mechanism for distribution of mitochondria during cell division in budding yeast. Curr Biol. 9:1111-1114. PMID: 10531006.

9. Boldogh, I., Vojtov, N., Karmon, S.L., and Pon, L.A. (1998). Mmm1p and Mdm10p, two integral mitochondrial outer membrane proteins, are required for interaction between mitochondria and the actin cytoskeleton in vitro and in vivo in budding yeast. J Cell Biol. 141:1371-1382. PMID: 13679517.

10. Lazzarino, D.A., Boldogh, I., Smith, M.G., Rosand, J. and Pon, L.A. (1994). ATP-sensitive, reversible actin binding activity in isolated yeast mitochondria. Mol Biol Cell. 5:807-818. PMID: 7812049. This study provided the first evidence that an organelle within yeast (mitochondria) co-localizes with actin cables and has actin binding activity. It laid the foundation for our current knowledge that virtually all cargos in yeast (e.g. ER, Golgi, vacuoles, peroxisomes, secretory vesicles, and mRNA) use actin cables as tracks for movement.

D. Research Support.

Active Mitochondrial-cytoskeletal interactions and aging funded by NIH/NIGMS, 1RO1GM096445 (PI: L. Pon)

12/01/10-11/30/15. Senior scholar award in aging funded by the Ellison Medical Foundation, AG-SS-2465-10 (PI: L.Pon) 10/1/10-

9/30/14. Mitochondrial motility and inheritance funded by NIH-NIGMS, 5RO1GM045735 (PI: L. Pon) 8/19/13-4/30/17. Super-resolution structured illumination microscope funded by the NIH, 1S10OD014584 (PI: L. Pon) 3/19/12 –

6/19/13. Confocal and Specialized Microscopy Core funded by NIH/NCI 5 P30 CA13696-35 (PI: R. Dalla-Favera) 7/1/08

- 6/30/13.

Course Evaluation 2013 Science Research Conferences

Mitochondrial Biogenesis and Dynamics inHealth Disease and Agingpresented 6/16/201354 forms submitted

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Forms

Section 1 - Scientific Content

General Sessions

The most important areas of current active research were adequately discussed. 4.5

There was a sufficient amount of unpublished research presented. 4.1

The conference helped you generate new ideas for research. 4.6

There was adequate time provided for invited presentations and short talks selected from submitted abstracts. 4.6

The discussion periods were utilized effectively. 4.4

Poster Sessions

The time allocated for poster sessions was effective. 4.2

I am satisfied with the contribution of the poster sessions to the conference. 4.2

Scientific Content - Overall

Overall, I am satisfied with the scientific content. 4.6

What kinds of sessions would you like to see included at future conferences?

apoptosis

Mitochondrial Transporters and diseases

mitochondrial respiratory chain assemblymitochondria-ER interaction

Perhaps more sessions on mitochondria and disease, and a bit less basic research.

Depending upon the quality of submitted abstracts, more talks from selected posters could be useful.

More OXPHOS assembly as the original theme of the conference

Mitochondrial translation and metabolism.

The title of the conference included mitochondrial dynamics but only one session touched on this topic. I attended the conferencespecifically for the mitochondrial dynamics aspect and would have been happier if half the conference was dedicated to this topic.

Excellent selection of diverse topics

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bioenergetics and redox biology

regulation, post-translational modifications, cell signaling

more biogenesis, more molecular mechanism

nucleo-mitochondrial interactions and signaling

I would like to have more focus on mitochondria to ER/SR communication as well as mitochondria nucleus signaling/interaction.

Continue to cover topics across a broad range of mitochondrial biology.

Mechanisms in biogenesis of the OXPHOS system

Mitochondrial lipid homeostasis. More on mitochondrial biogenesis.

Section 2 - Management

Program Management & Organization

How satisfied were you with the coordination and organization of the scientific program? 4.6

How satisfied were you the representation of international scientists in this field participating? 4.6

How satisfied were you with the conference materials provided? 4.4

Did you feel the length of conference sessions were too long, just about right, or too short? 2.4

(3=Too long; 2= Just about right; 1=Too short)

Logistics Management & Organization

How satisfied were you with the registration and abstract submission process? 4.4How satisfied were you with the information found on the FASEB SRC website and from emails sent by the FASEB SRCOffice? 4.2

Overall Management & Organization

The conference was well organized. 4.5

Conference onsite staff member was helpful and courteous. 4.4

Overall, I was satisfied with the conference facilities. 4.4

Where would you like to see future SRCs take place?

Europe

Oregon, Bahama

chicago

I think Montana was a very nice place. Maybe something around San Francisco - Monterey could be also nice.

in Europe

North eastern US, Chicago or other major midwest cities, West Coast. Ease of travel and reduction of travel costs are a bigconsideration.

South Florida, Washington, DC, California

Europe

In any pace that can be reached in less than 15 hours from overseas (this time: > 20 hours)

better to reach by direct flights from Europe (i.e. East coast)

Chicago

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Big Sky is a nice venue. However the conference room was often interrupted with extraneous noise from the kitchen or constructionwork elsewhere in the building.

Miami

Vermont

Steamboat Springs, CO, Snowmass, CO, Gleneden Beach, OR.

Which months are more convenient for you to attend a conference?

June - August: 28 (56%)

March - May: 11 (22%)

September - November: 7 (14%)

December - February: 4 (8%)

Overall, how would you rate the FASEB SRC Staffs' professionalism and responsiveness to your questions and concerns? 4.4

Comments:

Drs. Shadel and Manfredi were great.

It would be great if a registration would be possible without credit carte payment, since european institutes do not possess creditcartes. The meeting was announced (3 months before) very late, so that I could not ask for travel grants any more (most of them are4 months in advance).The staff was very unflexible: there was largely enough space for all posters, however we were asked to hang them down, which wasannoying during the discussion.

Before the early bird deadline the rooms were filled blocking registration of one participant in my group meaning that I had to pay thelate fee after contacting the FASEB office the following week. This was a minor issue but given many more registrants later bookedand a shared room was requested it was an inconvenience

Section 3 - General Information

Approximately how many conferences of this type do youattend annually?

1-2 per year: 36 (67.9%)

3-4 per year: 11 (20.8%)

5-6 per year: 4 (7.5%)

More than 6 per year: 1 (1.9%)

Don't usually attendconferences: 1 (1.9%)

Do you plan to attend this conference again in 2 or 3 years?

Yes: 46 (90.2%)

No: 5 (9.8%)

Would you recommend this conference to others?

Yes: 52 (96.3%)

No: 0 (0%)

Not Sure: 1 (1.9%)

No response: 1 (1.9%)

How would you rate this conference compared toother conferences of this type that you haveattended?

4.3

How did you learn of this conference?

Co-Worker: 19 (35.2%)

By Invitation: 17 (31.5%)

Internet: 9 (16.7%)

FASEB Mailings: 5 (9.3%)

FASEB Emails: 4 (7.4%)

Other: 0 (0%)

FASEB Journal: 0 (0%)

Experimental Biology/Neuroscience/Cell Biology: 0 (0%)

Please indicate your age group:

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20's: 2 (3.7%)

30's: 23 (42.6%)

40's: 14 (25.9%)

50's: 11 (20.4%)

60's: 4 (7.4%)

70's: 0 (0%)

In what ways could this conference be improved?

more accessible locationimprove food quality

Second 'poster' session is unnecessary

The poster session could have been better organized.

I think a few more translational research presentations could be beneficial, but I agree that it is not the priority of this type ofmeeting, because there are many clinical meetings.

Serious improvments could be done regarding the food and to have a more festive dinner at the last evening.

"Meet the experts session" was a disaster. Nobody was there.There was no planned group activities during afternoon brakes.Poster secctions was poorly attended in particular days 3 and 4.Poster seccion is more beneficial when all posters are dysplayed during the whole conference

More emphasis on Mitochondrial Biogenesis and complex assembly, which makes this conference unique and to avoid overlapping withmany other meetings.

more talks on mitochondrial dynamics. more talks from students and postdocs. too many of the older faculty spent the majority oftheir talks covering their published work over the past decade.

It would be better if it were a shorter meeting with less free time or less science.

Put the abstracts in order of the talks given. The short talks abstracts that were selected from the submissions were not listed withthe invited speakers and not identified in the program which made it difficult to find the abstract during the talks.

present more unpublished data (some presenters cited papers from 5 to 10 years ago as the main part of their talk), more mealchoices (especially for breakfast)

All the posters should have been up for the entire conference.

Food could have been better.

I think the addition of small group sessions to facilitate group discussions would be helpful instead of just presentations.

Also, I think that to incorporate the involvement of more participants it may be beneficial to have poster presentation or oralpresentation, not both.

I think it was great to divide the poster presentations into two day segments but it may be helpful to have the posters up for twodays and further divide the presentations (i.e. half of the Monday-Tuesday group would present on that Monday, half on that Tuesdayand the same pattern for the Wed Thurs poster group). I thought it was difficult to spend time at the posters I was interested induring the time allotted with the presenter there.

Incorporate more vegetarian options.

Conference sessions should end at 9pm rather than 10pm

possibility of organized group activities

Not much. Good mix of model systems and MRO's (medically relevant organisms) covering many areas. A basic session onmitochondria and PCD without getting too clinical.

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FINAL REPORT NOT AVAILABLE

Year# of

Applicants# of

Participants Commercial Non-

Commericial Government Total Raised2007 104 101 2,500.00$ 10,000.00$ 12,500.00$ 25,000.00$ 2009 85 84 1,000.00$ 48,203.00$ 25,000.00$ 26,000.00$ 2011 104 101 3,150.00$ 4,500.00$ 6,000.00$ 13,650.00$ 2013 114 110 24,775.00$ 5,000.00$ 29,775.00$

ATTENDANCE FUNDING

Mitochondrial Biogenesis and Dynamics in Health, Disease and AgingComparison of Previous Conferences

Year Name Affiliation2007 Dennis Winge Univ. of Utah

Eric Shoubridge Montreal Neurological Institute

2009 Carla Koehler UCLAThomas Langer Univ. of Cologne

2011 Antoni Barrientos University of MiamiRosemary Stuart Marquette University

2013 Gerald S. Shadel Yale UniversityGiovanni Manfredi Cornell University

Mitochondrial Biogenesis and Dynamics in Health, Disease and AgingPast Conference Organizers

December 5, 2011 Dr. Gerald Shadel Yale University School of Medicine Depts. of Pathology and Genetics 310 Cedar Street New Haven, CT 06520 USA Re Proposal #: 13-22 Dear Dr. Shadel: We would like to thank you for submitting a proposal for the 2013 FASEB Summer Research Conference series. After careful consideration by the Advisory Committee, the proposal entitled, "Mitochondrial Biogenesis and Dynamics in Health, Disease and Aging" has been tentatively approved. The committee would like you to respond by Thursday, December 15, 2011 to the following comments/concerns before they will fully approve the proposal:

• The committee asks that you form a plan for continuity in leadership. A successful plan includes a co-organizer of the conference becoming the main organizer for the next conference. A leadership plan ensures the conference’s continued success in terms of the program, advertising, and fundraising.

• The committee requests a more detailed plan for the Meet the Expert

session and the poster sessions. Please note that the Meet the Expert session is a time for attendees (especially students/junior investigators) to meet and network with the “experts” of your program.

• After reviewing your program, the committee found it limited.

Therefore, they request that you change your program to cover the entire scope of the field.

• The committee also requests that you form a plan to increase

fundraising as it did drop this past year. The support of the last three conferences is as follows:

Year

Non-Commericial Commercial Government Total Raised

2007 $2,500.00 $10,000.00 $12,500.00 $25,000.00 2009 $1,000.00 $48,203.00 $25,000.00 $26,000.00 2011 $3,150.00 $4,500.00 $6,000.00 $13,650.00

Fundraising is key to reimbursing speakers and assisting junior investigators and students.

Dr. Shadel Page 2 The committee requests that you make every effort to include young investigators (poster presentation or a short talk) as early as possible within the conference agenda. This will have an enormous impact on one’s experience at the conference. This will also allow other participants to learn early on about their work and will then greatly increase interaction. We will soon begin the process of developing the conference schedule and will let you know the location and date of your conference as soon as this has been decided. Please keep in mind, location and date preferences are not guaranteed however we do our best to give you your first choice. In February, an Organizer Manual will be posted at our website (www.faseb.org/SRC) to assist you in your conference planning efforts. Please be aware that by agreeing to be an Organizer/Co-organizer of a FASEB Summer Research Conference, that should you decide to cancel the conference for any reason, you will be held responsible for any fees related to the cancellation (i.e., fees charged by the host location). The Summer Research Conferences have been very successful over the years due to the commitment and dedication of the Organizers. On behalf of the Federation and the Summer Research Conferences Advisory Committee, your efforts in contributing to the success of the program are sincerely appreciated. A copy of this letter has also been sent to your co-organizer(s). Please do not hesitate to contact the SRC office by telephone at (301) 634-7010 or via the emails listed below with any questions. We look forward to working with you on this project over the next few years. Sincerely,

Jessica Lyons Conference Manager FASEB Summer Research Conferences jlyons@faseb.org

Emily Benson Conference Manager FASEB Summer Research Conferences ebenson@faseb.org

Robin Crawford Conference Manager FASEB Summer Research Conferences rcrawford@faseb.org

12/12/2011

Response to FASEB Advisory committee comments: • The committee asks that you form a plan for continuity in leadership. A successful plan includes a co-organizer of the conference becoming the main organizer for the next conference. A leadership plan ensures the conference’s continued success in terms of the program, advertising, and fundraising. Response. Our intention is to follow the leadership plan that has been utilized for this conference in the past. Historically, there have been two co-chairs of the conference that contribute more-or-less equally to the organization and fundraising. Hence no precedent has been established for a chair/co-chair relationship in which the chair does the majority of the organizing and the co-chair is responsible for leading the subsequent conference. For example, Antoni Barrientos and Rosemary Stuart were the co-chairs of the 2011 conference and neither is involved in the organization of the proposed 2013 conference. It was in this context that Dr. Manfredi and I agreed to co-chair the 2013 conference. As was the case for our “election,” two suitable co-chair candidates will be identified at the conference itself based on their stature in the field and desire to volunteer. Co-organizers from previous conferences have already been helpful in providing insight, materials on funding, etc., Dr. Manfredi and I will continue in this tradition. •The committee requests a more detailed plan for the Meet the Expert session and the poster sessions. Please note that the Meet the Expert session is a time for attendees (especially students/junior investigators) to meet and network with the “experts” of your program. Response. We will be modeling the “Meet the Expert” session after that which occurred at the last conference, which was successful. During one afternoon, individual tables in the lecture hall (or other suitable location) will be made available for all platform speakers to meet with interested parties. There was feedback provided from the last conference that this session be held later in the conference so that most of the speakers would have already been heard. As indicated in our program, this will held in the afternoon on the last day (Thursday), so that only one session remains that would not have been heard. This event will be advertised several times at the sessions and we will let speakers know in advance that they will be required to participate. There will be two poster sessions, which will occur from 4-6 PM between session 1 and 2 and between sessions 3 and 4. If a logical thematic grouping is evident, we will divide the posters accordingly, otherwise, a typical odd number (session 1)/even number (session 2) system will be used. • After reviewing your program, the committee found it limited. Therefore, they request that you change your program to cover the entire scope of the field. Response. Actually, we largely disagree. The program covers import, assembly, mtDNA expression, calcium signaling, dynamics (fusion/fission), apoptosis, signaling, reactive oxygen species, mitochondrial genetics, mitochondrial diseases, and the role of mitochondria in aging and longevity. Thus, we argue the program is sufficiently broad and is even attempting to bring out new aspects/subjects of mitochondria in cell biology and disease pathology (see session 8), which will

make for a cutting-edge meeting. Perhaps the committee is referring to a bigger emphasis on genetics and disease compared to the last conference? This was purposeful, as feedback from the last conference was that genetics and disease was under-represented, so we attempted to remedy this. In reality, the field has grown to include so many aspects of cell biology and disease that, at this point, it is an impossible task to cover the “entire scope of the field” in one meeting. If the committee has specific suggestions, we would ask for them to forward a list to us and we will try to oblige. We will also attempt to bring in other subjects (i.e. broaden the scope further) through the selection of abstracts for short talks on unrepresented aspects. • The committee also requests that you form a plan to increase fundraising as it did drop this past year. Response. These are trying times for science funding, but we shall do our best. At the end of last meeting, Dr. Manfredi was approached by Dr. Vernon Anderson, Program Director, Division of Pharmacology, Physiology and Biological Chemistry at NIGMS, who has indicated interest in us submitting a proposal to his Institute, if more emphasis were placed on disease in the 2013 meeting. This is one of the compelling reasons for the emphasis that we placed on this topic in the submitted program. Thus, we are encouraged on this front in terms of potential governmental funding from NIH. Since we are also having a session on aging, we will solicit funding from aging foundations, such as the Glenn Foundation and AFAR, as well as NIA. Since we are including the role of mitochondria in disease, we will also contact individual foundations that advocate in favor of research on neurodegeneration and other diseases, such as ALS Association, the Robert Packard Research Center for ALS Research, The Friedreich’s Ataxia Research Alliance, The United Mitochondrial Disease Foundation, and others. Finally, we will approach private and pharmaceutical companies interested in mitochondrial reagents and therapeutics for contributions. Please let us know if we can clarify anything else, Gerald S. Shadel and Giovanni Manfredi Co-organizers, 2013 FASEB meeting on “ Mitochondrial Biogenesis and Dynamics in Health, Disease and Aging”