Mitochondrial Biology: New Perspectives: Novartis Foundation Symposium 287

252 Pages·2007·10.172 MB·English

by  Novartis Foundation(eds.)

Mitochondrial Biology: New Perspectives: Novartis Foundation Symposium 287, Volume 287.
Edited by Derek J. Chadwick and Jamie Goode
Copyright  Novartis Foundation 2007. ISBN: 978-0-470-06657-7
MITOCHONDRIAL BIOLOGY:
NEW PERSPECTIVES
The Novartis Foundation is an international scientifi c and educational
charity (UK Registered Charity No. 313574). Known until September 1997
as the Ciba Foundation, it was established in 1947 by the CIBA company of
Basle, which merged with Sandoz in 1996, to form Novartis. The
Foundation operates independently in London under English trust law. It
was formally opened on 22 June 1949.
The Foundation promotes the study and general knowledge of science and
in particular encourages international co-operation in scientifi c research.
To this end, it organizes internationally acclaimed meetings (typically eight
symposia and allied open meetings and 15–20 discussion meetings each
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Novartis Foundation Symposium 287
MITOCHONDRIAL
BIOLOGY: NEW
PERSPECTIVES
Copyright © Novartis Foundation 2007
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Novartis Foundation Symposium 287
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Contents
Symposium on New perspectives on mitochondrial biology, held at the Novartis Foundation,
London, 28–30 November 2006
Editors: Derek J. Chadwick (Organizer) and Jamie Goode
This symposium is based on a proposal by Michael Duchen
David G. Nicholls Chair’s introduction 1
Albert Neutzner, Richard J. Youle and Mariusz Karbowski
Outer mitochondrial membrane protein degradation by the proteasome 4
Discussion 14
Sarah E. Haigh, Gilad Twig, Anthony A. J. Molina, Jakob D. Wikstrom,
Motti Deutsch and Orian S. Shirihai PA-GFP: a window into
the subcellular adventures of the individual mitochondrion 21
Discussion 36
Luca Scorrano Multiple functions of mitochondria-shaping proteins 47
Discussion 55
Bruce M. Spiegelman Transcriptional control of mitochondrial energy
metabolism through the PGC1 coactivators 60
Discussion 63
Charles Affourtit, Paul G. Crichton, Nadeene Parker and Martin D. Brand
Novel uncoupling proteins 70
Discussion 80
Cecilia Giulivi Mitochondria as generators and targets of
nitric oxide 92
Discussion 100
György Hajnóczky, Masao Saotome, György Csordás, David Weaver and
Muqing Yi Calcium signalling and mitochondrial motility 105
Discussion 117
v
vi CONTENTS
Anna Romagnoli, Paola Aguiari, Diego De Stefani, Sara Leo,
Saverio Marchi, Alessandro Rimessi, Erika Zecchini, Paolo Pinton
and Rosario Rizzuto Endoplasmic reticulum/mitochondria calcium
cross-talk 122
Discussion 131
Brian O’Rourke, Sonia Cortassa, Fadi Akar and Miguel Aon
Mitochondrial ion channels in cardiac function and dysfunction 140
Discussion 152
Paolo Bernardi and Michael Forte The mitochondrial permeability
transition pore 157
Discussion 164
Dominic James, Philippe A. Parone, Olivier Terradillos,
Safa Lucken-Ardjomande, Sylvie Montessuit and
Jean-Claude Martinou Mechanisms of mitochondrial outer membrane
permeabilization 170
Discussion 176
M. Flint Beal Mitochondria and neurodegeneration 183
Discussion 192
Mügen Terzioglu and Nils-Göran Larsson Mitochondrial dysfunction in
mammalian ageing 197
Discussion 208
Eric A. Schon and Salvatore DiMauro Mitochondrial mutations: genotype
to phenotype 214
Discussion 226
Contributor Index 234
Subject index 236
Participants
Vera Adam-Vizi Department of Medical Biochemistry, Semmelweis University,
PO Box 262, H-1444 Budapest, Hungary
M. Flint Beal Department of Neurology and Neuroscience, Weill Medical College
of Cornell University, 525 East 68th Street, Room F610, New York, NY 10021,
USA
Piotr Bednarczyk (Novartis Foundation Bursar) Department of Biophysics, Agri-
cultural University SGGW, 159 Nowousynowska St., 02-776 Warsaw, Poland
Paolo Bernardi Department of Biomedical Sciences, Università di Padova, Viale
Giuseppe Colombo 3, I-35121 Padova, Italy
Martin D. Brand MRC Dunn Human Nutrition Unit, Hills Road, Cambridge
CB2 2XY, UK
Michael Duchen Department of Physiology, University College London, Gower
Street, London, WC1E 6BT, UK
Cecilia Giulivi Department of Molecular Biosciences, University of California,
1311 Haring Hall, One Shields Avenue, Davis, CA 95616, USA
György Hajnóczky Department of Pathology, Anatomy and Cell Biology, Thomas
Jefferson University, Rm 253 7AH, 1020 Locust Street, Philadelphia, PA 19107,
USA
Andrew P. Halestrap Department of Biochemistry, School of Medical Sciences,
University of Bristol, Bristol BS8 1TD, UK
Derek Hausenloy (Novartis Foundation Bursar) The Hatter Cardiovascular Insti-
tute, University College Hospital, 67 Chenies Mews, London WC1E 6HX,
UK
Howard T. Jacobs Institute of Medical Technology, University of Tampere, FI
33014, Finland
vii
viii PARTICIPANTS
Nils-Göran Larsson Karolinska Institutet, Department of Laboratory Medicine,
Division of Metabolic Diseases, Novum, S-14186 Stockholm, Sweden
John J. Lemasters Pharmaceutical Sciences and Biochemistry & Molecular
Biology, Medical University of South Carolina, QF308 Quadrangle Building,
280 Calhoun Street, PO Box 250140, Charleston, SC 29425, USA
Jean-Claude Martinou Department of Cell Biology, Sciences III, University of
Geneva, 30 quai Ernest Ansermet, 1211 Geneva 4, Switzerland
David G. Nicholls (Chair) Morphology Core, Buck Institute for Age Research,
8001 Redwood Blvd, Novato, CA 94945, USA
Brian O’Rourke School of Medicine, Institute of Molecular Cardiobiology, The
Johns Hopkins University, 720 Rutland Avenue, 1059 Ross Bldg., Baltimore,
MD 21205-2195, USA
Sten Orrenius Institute of Environmental Medicine, Division of Toxicology,
Karolinska Institutet, Box 210, Stockholm, SE-171 77, Sweden
Anant Parekh Department of Physiology, Anatomy and Genetics, University of
Oxford, Parks Road, Oxford, OX1 3PY, UK
Ian J. Reynolds Merck Research Laboratories, WP42-229, 770 Sumneytown Pike,
P O Box 4, West Point, PA 19486-0004, USA
Peter R. Rich The Glynn Laboratory of Bioenergetics, Department of Biology,
University College London, Gower Street, London WC1E 6BT, UK
Rosario Rizzuto Department of Experimental and Diagnostic Medicine, General
Pathology Section, University of Ferrara, Via L. Borsari 46, 44100 Ferrara,
Italy
Eric A. Schon Department of Neurology, Room 4-431, College of Physicians and
Surgeons, Columbia University, 630 West 168th Street, New York, NY 10032,
USA
Luca Scorrano Dulbecco-Telethon Institute, Venetian Institute of Molecular
Medicine, Via Orus 2, Padova, I-35129, Italy
PARTICIPANTS ix
Orian Shirihai Department of Pharmacology and Experimental Therapeutics,
Tufts University School of Medicine, 136 Harrison Avenue, Boston, MA 02111,
USA
Bruce M. Spiegelman Dana-Farber Cancer Institute and Department of Cell
Biology, Harvard Medical School, Boston, MA 02115, USA
Douglas M. Turnbull Mitochondrial Research Group, School of Neurology,
Neurobiology and Psychiatry, The Medical School, Newcastle University,
Newcastle Upon Tyne, NE2 4HH, UK
Richard J. Youle Biochemistry Section, Surgical Neurology Branch, National
Institutes of Health, Bldg 35, Room 2C917, 25 Convent Drive, MSC 370,
Bethesda, MD 20892, USA
Mitochondrial Biology: New Perspectives: Novartis Foundation Symposium 287, Volume 287.
Edited by Derek J. Chadwick and Jamie Goode
Copyright  Novartis Foundation 2007. ISBN: 978-0-470-06657-7
Chair’s introduction
David G. Nicholls
Buck Institute for Age Research, 8001 Redwood Blvd, Novato, CA 94945, USA
In this introduction I want to summarize where we are in the fi eld and where we
are going. What is the future of mitochondrial bioenergetics? A couple of weeks
ago I had an idle moment, so I logged on to PubMed and entered the search term
‘mitochondria’ followed by the years 1950 and 2006, one after the other. The
results were fascinating. The numbers of citations per year for mitochondria started
off in the bioenergetic prehistory, going back almost 100 years to the fi rst descrip-
tions of mitochondria. For me, the single event that introduced the classic era of
mitochondrial bioenergetics was the publication of papers by Chance and Williams
in the mid 1950s which fi rst described the oxygen electrode, and described the
redox changes of the cytochromes. What happened then was an explosive growth
over the next 10 or 15 years in the number of papers, which led to over 3000 papers
per year by the time the next revolution came. This was Peter Mitchell’s work in
the late 1960s. This is interesting: whereas you would expect that the discovery of
a mechanism would stimulate a lot of new research, what happened after the three
or four years when Peter was publishing these fantastic papers is that the fi eld
stagnated for 20 years in terms of numbers of publications. Somehow, because
bioenergetics had defi ned itself so narrowly in terms of understanding how the
respiratory chain and ATP synthase works with a little bit of ion transport, this
limited the fi eld.
The next explosion of research came when our cell biology colleagues working
on cell health and death discovered, sometimes to their discomfort, that mitochon-
dria moved into the centre of the fi eld. In the last 10 years the trend has been
almost explosive in terms of the number of papers on mitochondrial bioenergetics.
I didn’t have time to do a statistical sampling of the different years, but my guess
is that 80% of these papers come under the fi eld of mitochondrial physiology:
mitochondria in the context of the cell.
What is interesting is where we are going. To quote Donald Rumsfeld, it is the
unknown unknowns that will defi ne where the fi eld moves in the next 10 years.
In 1994, no one knew that they didn’t know how cytochrome c was released,
because it wasn’t part of the vocabulary. What does this have to do with cell death?
It is the things that we don’t know that we don’t know which are going to defi ne
the next 10 years or so.
1