Mitochondrial Physiology Network 10.9: 1-146 (2005) Last update: 2005-08-29 Mitochondrial Physiology The Many Faces and Functions of an Organelle Edited by Erich Gnaiger MiP2005 MiP 4th Conference on Mitochondrial Physiology Schröcken, Vorarlberg, Austria MiP – Mitochondrial Physiology www.mitophyisology.org 2 MiP2005 Organization MiP Board Mitochondrial Physiology Society Chair Erich Gnaiger (Innsbruck, Austria) Co-Chairs Guy Brown (Cambridge, United Kingdom) Cecilia Giulivi (Davis, USA) Eiji Takahashi (Yamagata, Japan) Steven Hand (Baton Rouge, USA) Local Organizers Erich Gnaiger (Innsbruck, Austria) Eveline Hütter (Innsbruck, Austria) Brigitte Haffner (Innsbruck, Austria) Advisory Board Susanne Arnold (Berlin, Germany) Vilma Borutaite (Cambridge, United Kingdom) Robert Boushel (Montreal, Canada) Susana Cadenas (Madrid, Spain) Keith Garlid (Oregon, USA) Charles Hoppel (Cleveland, USA - UMDF) Josef Houstek (Prague, Czech Republic) Pidder Jansen-Dürr (Innsbruck, Austria) Bernhard Kadenbach (Marburg, Germany) Andrey Kozlov (Vienna, Austria) Thierry Letellier (Bordeaux, France) Heimo Mairbäurl (Heidelberg, Germany) Heinz Osiewacz (Frankfurt, Germany) Sergio Papa (Bari, Italy) Richard Porter (Dublin, Ireland) Rodrigue Rossignol (Bordeaux, France) Patrick Schrauwen (Maastricht, The Netherlands) Vladimir Skulachev (Moscow, Russia) Francis Sluse (Liège, Belgium) Anibal Vercesi (Campinas, Brasil) Lech Wojtczak (Warszawa, Poland) Cooperation Competence Centre Medicine Tyrol OROBOROS INSTRUMENTS Focus Continuing rigorous mitochondrial bioenergetics; integrating molecular, cellular and organismic physiology and pathology - mitochondrial function in health and disease. Presentations by established scientists and young investigators. In the face of a tremendously increased interest in MiP2005, the max. number of participants was increased from 100 to 160. Irrespectively, the number of oral presentations remains limited to provide time for discussions. The 3rd MiP Conference was held in 2003 (Schröcken, Austria), at which occasion the MiP Society was formed. With your on-line registration, you may choose to become a member of the MiP Society: www.mitophysiology.org Mitochondrial Physiology – MiP2005 www.mitophyisology.org 3 Mitochondrial Physiology MiP Society Continuing a tradition of rigorous mitochondrial bioenergetics Integrating molecular, cellular and organismic physiology and pathology Mitochondrial Physiology www.mitophysiology.org The Mitochondrial Physiology Socienty has been founded in 2003, to organize MiP Conferences and MiP Workshops. These “MiP Events” focus on common and cell-specific functions of mitochondria at molecular, organelle, cellular, tissue and organ levels. Thus we meet the increasing demands for integrating current developments in the methodologically and conceptually complex field of mitochondrial physiology. Mitochondrial research has recently undergone a dramatic renaissance, due to a whole series of discoveries revealing its central roles in cell death, disease pathology, aging, thermogenesis, oxidative stress, cell signalling, cellular regulation and cell bioenergetics. Functional genomics and proteomics is putting an urgent emphasis on integrative understanding of the link between genes/molecules and cellular/organisms functions. Because these topics require continuous technical advances there will also be an emphasis on new methodological developments, quantitative methods of analysis in mitochondrial research including mathematical modeling, proteomics and the use of tools for measuring multiple parameters in an experiment. This multidisciplinary approach requires a new forum for high-level training courses, bringing together scientists working in divergent disciplines, to talk together about mitochondrial function and dysfunction, to resolve differences, to develop research agendas, to spread new knowledge and techniques, and to develop collaborations. Until recently, mitochondrial respiratory function was mainly studied in research laboratories specializing on the bioenergetics of isolated mitochondria and bacteria, energy transformation in transmembrane gradients and characterization of the various complexes of the respiratory chain. Today these methods and concepts are expanded to applications on intact or permeablized cells and tissue preparations, and are widely used by groups with different research and clinical orientation, particularly in molecular cell signalling. The series of MiP Events will help to provide the expertise necessary for successful application of the techniques and concepts on mitochondrial bioenergetics in the wider context of molecular and cell biology, exercise physiology, diagnosis of mitochondrial diseases, and evaluation of mitochondrial function in oxidative stress, ischemia-reperfusion, aging and numerous areas (such as apoptosis) of key-involvement of mitochondria. Erich Gnaiger, Ph.D. Guy Brown, Ph.D. Chairman, MiP Society Co-Chairman, MiP Society Department of Transplant Surgery Department of Biochemistry D. Swarovski Research Laboratory University of Cambridge Innsbruck Medical University Tennis Court Rd Innrain 66/6 Cambridge CB2 1QW, UK A-6020 Innsbruck, Austria Tel: +43 512 504 24623 (24626) T +44 1223 766055 Fax: +43 512 504 24625 F +44 1223 333342 E-mail: [email protected] E-mail: [email protected] URL: www.mitophyisology.org Mitochondrial Physiology – MiP2005 www.mitophyisology.org 4 MiP2005 Chairpersons receive a MiP2005 present if their session is successfully started and completed within the time scheduled in the programme, and if they guide discussions such that contributions are made to clarify what MiP is. 10+5 min Presentations: Speakers receive a MiP2005 present if their presentation proves that they selected their 10 (max. 12) best slides, if the PowerPoint slides are readable from the far back, and if transmission of the key message for MiP is completed within 600 s (use of SI units is encouraged). +5 min will be reserved for discussions. This should particularly provide poster presenters an additional opportunity to point out connections to their related messages. Posters receive a MiP2005 present if the poster reveals focus on the essential detail and visible perspective on MiP. YIP - Young Investigator Presentations: Students are invited to participate in the competition for YIP awards. (1) Selection of a YIP for a 10+5 min oral presentation is a MiP award, based on submitted abstracts. (2) Six YIP posters are selected during the meeting for 5-min presentations in Session 12 (5+5 min), and these young investigators receive MiP awards. Instrument Exhibition: Specific instrument exhibitions are organized in the lunch breaks and evenings, in connection with poster presentations. Mitochondrial Physiology – MiP2005 www.mitophyisology.org 5 Table of Contents Mitochondrial Physiology Board .......................................................... 2 Mitochondrial Physiology and MiP2005 ................................................ 3 United Mitochondrial Disease Foundation ............................................. 7 Opening: Mitochondrial Physiology: The Many Faces and Functions of an Organelle ................................................ 9 Session 1: Integrated Cardiovascular and Mitochondrial Physiology - I. Skeletal Muscle, Exercise, and Endurance ........................... 13 Session 2: Integrated Cardiovascular and Mitochondrial Physiology - II. Oxygen Delivery, Hypoxia, and Altitude ............................. 23 Session 3: Signalling To and From the Mitochondria - I. Nitric Oxide and Calcium .................................................. 33 Session 4: Signalling To and From the Mitochondria – II. .................................... 45 Session 5: Organization of the Mitochondrial Respiratory Chain and Control of Oxidative Phosphorylation ............................... 55 Session 6: Respiration, Coupling, Permeability Transition, and UCPs ..................... 69 Session 7: Oxidative Stress and Mitochondrial Function ...................................... 83 Session 8: Mitochondria in Ischemia-Reperfusion and Cardiomyopathy ................. 95 Session 9: Mitochondria and Degenerative Diseases – I. Animal Models ...............................................................103 Session 10: Mitochondria and Degenerative Diseases – II. Patients and Human Cell Lines ........................................113 Session 11: Mitochondria and Aging .................................................................121 Session 12: Mitochondrial Physiology – an Integration .........................................131 Sponsors ....................................................................................133 Author Index ...............................................................................134 Addresses of Contributors and Participants ......................................136 Mitochondrial Physiology – MiP2005 www.mitophyisology.org 6 Walks and talks at MiP2003: Erich Gnaiger (top), Eiji Takahashi (left), Guy Brown and Cecilia Giulivi (middle), Evi Hütter and Steve Hand (right). Mitochondrial Physiology – MiP2005 www.mitophyisology.org 7 September 9, 2005 Dear Colleagues: On behalf of the Board of Directors and Staff of the United Mitochondrial Disease Foundation (UMDF), we are pleased to offer these words of congratulations and support. At UMDF, our mission is our driving force: To promote research and education for the diagnosis, treatment, and cure of mitochondrial disorders and to provide support for affected