Table Of ContentFrontiers of Cellular
Bioenergetics
Molecular Biology, Biochemistry,
and Physiopathology
Frontiers of Cellular
8 ioenergetics
Molecular Biology, Biochemistry,
and Physiopathology
Edited by
Sergio Papa and
Ferruccio Guerrieri
University of Bari
Bari, Italy
and
Joseph M. laser
University of Amsterdam
Amsterdam, The Netherlands
SPRINGER SCIENCE+BUSINESS MEDIA, LLC
Library of Congress Cataloging in Publication Data
Frontiers of cellular bioenergetics: molecular biology, biochemistry, and physiopathology /
edited by Sergio Papa, Ferruccio Guerrieri, and Joseph M. Tager.
p. cm.
Includes bibliographical references and index.
ISBN 978-1-4613-7196-0 ISBN 978-1-4615-4843-0 (eBook)
DOI 10.1007/978-1-4615-4843-0
1. Energy metabolism. 2. Cell metabolism. 3. Bioenergetics. 4. Mitochondrial pathology.
1. Papa, S. (Sergio) II. Guerrieri, Ferruccio. III. Tager, J. M.
QP176.F76 1999 98-49078
572'.43-dc21 CIP
ISBN 978-1-4613-7196-0
© 1999 Springer Science+Business Media New York
Originally published by Kluwer Academic / Plenum Publishers in 1999
10987654321
A CI.P. record for this book is available from the Library of Congress.
AII rights reserved
No par! of this book may be reproduced, stored in a retrieval system, or transmitted in any
form or by any means, electronic, mechanical, photocopying, microfilming, recording, or
otherwise, without written permission from the Publisher
Contributors
L. Mario Amzel Department of Biophysics and Biophysical Chemistry, and
Department of Biological Chemistry, Johns Hopkins School of Medicine,
Baltimore, Maryland 21205
Susanne Arnold Fachbereich Chemie, Philipps-Universitat, D-35032 Mar
burg, Germany
Gerald T. Babcock Department of Biochemistry, Michigan State University,
East Lansing, Michigan 48824
J. A. Berden E. C. Slater Institute, BioCentrum, University of Amsterdam,
Plantage Muidergracht 12, 1018 TV Amsterdam, The Netherlands
Paolo Bernardi CNR Unit for the Study of Biomembranes, Department of
Biomedical Sciences, University of Padova Medical School, 1-35121
Padova, Italy
Mario A. Bianchet Department of Biophysics and Biophysical Chemistry,
and Department of Biological Chemistry, Johns Hopkins School of Medi
cine, Baltimore, Maryland 21205
Domenico Boffoli Institute of Medical Biochemistry and Chemistry, Univer
sity of Bari, 1-70124 Bari, Italy
Maurizio Brunori Department of Biochemical Sciences and CNR Center of
Molecular Biology, University of Roma "La Sapienza," 00185 Rome,
Italy
Gerard Buse Institut fUr Biochemie, Rheinisch-Westfalische Technische
Hochschule, 52057 Aachen, Germany
Palmiro Cantatore Department of Biochemistry and Molecular Biology,
University of Bari, 70125 Bari, Italy
Nazzareno Capitanio Institute of Medical Biochemistry and Chemistry,
University of Bari, 1-70124 Bari, Italy
v
vi Contributors
H. Cock Department of Clinical Neurosciences, Royal Free Hospital School
of Medicine, London NW3 2PF, England
Johann Deisenhofer Howard Hughes Medical Institute and Department of
Biochemistry, University of Texas, Southwestern Medical Center, Dallas,
Texas 75235
Kai-Ping Deng Department of Biochemistry and Molecular Biology, Okla
homa State University, Stillwater, Oklahoma 74078
Emilio D'Itri Department of Biochemical Sciences and CNR Center of
Molecular Biology, University of Roma "La Sapienza," 00185 Rome,
Italy
Stefan Exner Fachbereich Chemie, Philipps-Universitiit, D-35032 Marburg,
Germany
Shelagh Ferguson-Miller Department of Chemistry, Michigan State Uni
versity, East Lansing, Michigan 48824
Adrian Flierl Wissenschaftliche Nachwuchsgruppe, Theodor-Boveri-Institut,
97074 Wtirzburg, Germany
Francesca Forti Division of Biochemistry and Genetics, National Neuro
"e.
logical Institute Besta," Milan 20133, Italy
Viola Frank Fachbereich Chemie, Philipps-Universitiit, D-35032 Marburg,
Germany
Masamitsu Futai Department of Biological Sciences, Institute of Scientific
and Industrial Research, Osaka University, Ibaraki, Osaka 567, Japan
Antonio Gaballo Institute of Medical Biochemistry and Chemistry, Univer
sity of Bari, 1-70124 Bari, Italy
Maria N. Gadaleta Department of Biochemistry and Molecular Biology,
University of Bari, 70125 Bari, Italy
Alessandro Giuffre Department of Biochemical Sciences and CNR Center
of Molecular Biology, University of Roma "La Sapienza," 00185 Rome,
Italy
Ferruccio Guerrieri Institute of Medical Biochemistry and Chemistry, and
Centre for the Study of Mitochondria and Energy Metabolism, University
of Bari, 70124 Bari, Italy
A. F. Hartog E. C. Slater Institute, BioCentrum, University of Amsterdam,
Plantage Muidergracht 12, 1018 TV Amsterdam, The Netherlands
Youssef Hateji Division of Biochemistry, Department of Molecular and Ex
perimental Medicine, The Scripps Research Institute, La Jolla, California
92037
Curtis W. Hoganson Department of Biochemistry, Michigan State Univer
sity, East Lansing, Michigan 48824
Gerhard Hummer Theoretical Biology and Biophysics Group, Los Alamos
National Laboratory, Los Alamos, New Mexico 87545
Maik Hiittemann Fachbereich Chemie, Philipps-Universitiit, D-35032 Mar
burg, Germany
Contributors vii
So Iwata Max-Planck-Institut fUr Biophysik, D-60528 Frankfurt am Main,
Germany
Anatoly M. Kachurin Department of Biochemistry and Molecular Biology,
Oklahoma State University, Stillwater, Oklahoma 74078
Bernhard Kadenbach Fachbereich Chemie, Philipps-Universitat, D-35032
Marburg, Germany
Hoeon Kim Howard Hughes Medical Institute and Department of Bio
chemistry, University of Texas, Southwestern Medical Center, Dallas,
Texas 75235
Angela M. S. Lezza Department of Biochemistry and Molecular Biology,
University of Bari, 70125 Bari, Italy
Dietmar Under Biochemisches Institut am Klinikum, Justus Liebig Univer
sitat, D-35385 Giessen, Germany
Thomas A. Link Universitatsklinikum Frankfurt, ZBC, Institut fUr Bio
chemie I, Molekulare Bioenergetik, D-60590 FrankfurtlMain, Germany
Rebecca Lucas Department of Chemistry, Michigan State University, East
Lansing, Michigan 48824
Hartmut Michel Max-Planck-Institut fUr Biophysik, D-60528 Frankfurt am
Main, Germany
Denise A. Mills Department of Chemistry, Michigan State University, East
Lansing, Michigan 48824
Joel E. Morgan Helsinki Bioenergetics Group, Department of Medical
Chemistry, Institute of Biomedical Sciences and Biocentrum Helsinki,
University of Helsinki, FI-OOOI4 Helsinki, Finland
Monica Munaro Division of Biochemistry and Genetics, National Neuro
logical Institute "C. Besta," Milan 20133, Italy
Peter Nicholls Department of Biological Sciences, Brock University, St.
Catharines, Ontario L2S 3Al, Canada; present address: Department of
Biological and Chemical Sciences, University of Essex, Wivenhoe Park,
Colchester C04 3SQ, England
Ben van Ommen Department of Pharmaco-Biology, Laboratory of Bio
chemistry and Molecular Biology, University of Bari, 1-70125 Bari, Italy
Hiroshi Omote Department of Biological Sciences, Institute of Scientific and
Industrial Research, Osaka University, Ibaraki, Osaka 567, Japan
Christian Ostermeier Max-Planck-Institut fUr Biophysik, D-60528 Frank
furt am Main, Germany
F erdinando Palmieri Department of Pharmaco-Biology, Laboratory of Bio
chemistry and Molecular Biology, University of Bari, 1-70125 Bari, Italy
Sergio Papa Institute of Medical Biochemistry and Chemistry, University of
Bari, 1-70124 Bari, Italy
Peter L Pedersen Department of Biophysics and Biophysical Chemistry,
and Department of Biological Chemistry, Johns Hopkins School of Medi
cine, Baltimore, Maryland 21205
viii Contributors
Harvey Penefsky State University of New York, Syracuse, New York 13210;
and Public Health Research Institute, New York, New York 10028
Vittoria Petruzzella Unit of Molecular Medicine, Children's Hospital "Bam
bino Gesu," Rome 00165, Italy
Jean-Paul di Rago Centre de Genetique Moleculaire, CNRS, 91190 Gif-sur
Yvette, France
Annette Reith Fachbereich Chemie, Philipps-UniversiHit, D-35032 Mar
burg, Germany
Peter R. Rich Department of Biology, University College, London WClE
6BT, England
Cecilia Saccone Department of Biochemistry and Molecular Biology,
C.S.M.M.E. CNR, University of Bari, 1-70125 Bari, Italy
Paolo Sarti Department of Biochemical Sciences and CNR Center of Mo
lecular Biology, University of Roma "La Sapienza," 00185 Rome, Italy
Richard C. Scarpulla Department of Cell and Molecular Biology, North
western Medical School, Chicago, Illinois 60611
A. H. V. Schapira Department of Clinical Neurosciences, Royal Free Hospi
tal School of Medicine, and Department of Clinical Neurology, Institute
of Neurology, London NW3 2PF, England
Martina Schliebs Wissenschaftliche Nachwuchsgruppe, Theodor-Boveri
Institut, 97074 WUrzburg, Germany
Ulrich Schulte Institut fUr Biochemie, Heinrich-Heine-Universitat, D 40225
DUsseldorf, Germany
Peter Seibel Wissenschaftliche Nachwuchsgruppe, Theodor-Boveri-Institut,
97074 WUrzburg, Germany
Sudha K. Shenoy Department of Biochemistry and Molecular Biology,
Oklahoma State University, Stillwater, Oklahoma 74078
Wenjun Shi Department of Biochemistry, Michigan State University, East
Lansing, Michigan 48824
Kyoko Shinzawa-Itoh Department of Life Science, Himeji Institute of Tech
nology, Kamigohri, Akoh Hyogo 678-12, Japan
Vladimir P. Skulachev Department of Bioenergetics, A. N. Belozersky Insti
tute of Physico-Chemical Biology, Moscow State University, Moscow
119899, Russia
Piotr P. Slonimski Centre de Genetique Moleculaire, CNRS, 91190 Gif-sur
Yvette, France
Abdul-Kader Souid State University of New York, Syracuse, New York
13210; and Public Health Research Institute, New York, New York 10028
Tewfik Soulimane Institut fUr Biochemie, Rheinisch-Westfalische Tech
nische Hochschule, 52057 Aachen, Germany
J.-W. Taanman Department of Clinical Neurosciences, Royal Free Hospital
School of Medicine, London NW3 2PF, England
Contributors ix
Bernard L. Trumpower Department of Biochemistry, Dartmouth Medical
School, Hanover, New Hampshire 03755
Tomitake Tsukihara Institute for Protein Science, Osaka University, Suita,
Osaka 565, Japan
Michaell. Verkhovsky Helsinki Bioenergetics Group, Department of Medi
cal Chemistry, Institute of Biomedical Sciences and Biocentrum Helsinki,
University of Helsinki, FI-00014 Helsinki, Finland
Gaetano Villani Institute of Medical Biochemistry and Chemistry, Univer
sity of Bari, 1-70124 Bari, Italy
Douglas C. Wallace Center for Molecular Medicine, Emory University
School of Medicine, Atlanta, Georgia 30322
Hanns Weiss Institut fiir Biochemie, Heinrich-Heine-Universitat, D 40225
Diisseldorf, Germany
Marten Wikstrom Helsinki Bioenergetics Group, Department of Medical
Chemistry, Institute of Biomedical Sciences and Biocentrum Helsinki,
University of Helsinki, FI-00014 Helsinki, Finland
William H. Woodruff Chemical Science and Technology Division, Los Al
amos National Laboratory, Los Alamos, New Mexico 87545
Di Xia Howard Hughes Medical Institute and Department of Biochemistry,
University of Texas, Southwestern Medical Center, Dallas, Texas 75235
Ting Xu Institute of Medical Biochemistry and Chemistry, University of
Bari, 1-70124 Bari, Italy. Permanent address: Institute of Biophysics,
Academia Sinica, Beijing, 100101, China
Shinya Yoshikawa Department of Life Science, Himeji Institute of Technol
ogy, Kamigohri, Akoh Hyogo 678-12, Japan
Chang-An Yu Department of Biochemistry and Molecular Biology, Okla
homa State University, Stillwater, Oklahoma 74078
Linda Yu Department of Biochemistry and Molecular Biology, Oklahoma
State University, Stillwater, Oklahoma 74078
Franco Zanotti Institute of Medical Biochemistry and Chemistry, Univer
sity of Bari, 1-70124 Bari, Italy
Massimo Zeviani Unit of Molecular Medicine, Children's Hospital "Bam
bino Gesu," Rome 00165, Italy
Li Zhang Department of Biochemistry and Molecular Biology, Oklahoma
State University, Stillwater, Oklahoma 74078
Yuejun Zhen Department of Chemistry, Michigan State University, East
Lansing, Michigan 48824
Foreword
One of the most obvious and fundamental properties of living things is their
ability to utilize the potential energy in their environment for their own ends. It
is not surprising therefore that the mechanism of this biotransformation of
energy-bioenergetics-has long exercised the minds of the leading scientists
of their day-from Lavoisier's recognition that respiration is fundamentally
the same as combustion, Priestley's discovery of photosynthesis, and Spallan
zani's thesis that respiration is an intracellular process.
Until about 30 years ago, the field of bioenergetics was the center of
biochemistry, attracting many of the great biochemists of the century, such as
Warburg, Keilin, Meyerhof, Engelhardt, Krebs, Lipmann, and Calvin. After the
main pathways of intermediary metabolism and electron transfer were estab
lished, however, further progress in elucidating the mechanistic details was
slow. This slowdown was due to the absence of sufficient knowledge of the
structure of the catalysts involved, even after the innovative proposal by
Mitchell on the fundamental role of the translocation of protons across mem
branes, which revolutionized the way in which the mechanism of energy
transduction was envisaged and for which he was awarded the Nobel Prize for
chemistry in 1978. Competition from other fields of biochemistry in which
progress was more spectacular has caused funding difficulties for those work
ing in bioenergetics.
Recently, however, significant advances in our knowledge of the structure
of most of the large proteins in energy-transducing membranes, even the very
large mammalian cytochrome c oxidase (Warburg's atmungsJerment), has
opened new perspectives for solving in fine detail the mechanism of electron
transfer and oxidative phosphorylation. This has been recognized in the award
of the Nobel prizes in chemistry in 1988 for the determination of the three-
xi
xii Foreword
dimensional structure of a photosynthetic reaction center and in 1997 for the
structure and mechanism of action of ATPases.
The detailed study of the properties of mitochondria and chloroplasts, the
energy-transducing organelles of respiration and photosynthesis, respectively,
led bioenergeticists in the 1960s to the discovery of extranuclear DNAs, func
tioning as a cytoplasmic genetic system, which was foreshadowed by Ephrussi.
In particular, the mitochondrial genome was found to code for a number of
hydrophobic membrane-associated subunits of the major proteins involved in
respiration and the oxidative phosphorylation, a finding that has greatly ex
tended the frontiers of bioenergetics. The discovery that certain rare inherited
human diseases are due to mutations in the mitochondrial DNA has opened up
the study of the physiopathology of mitochondria as a new frontier in bio
energetics. The hypothesis that random mutations during the course of a human
life is a component of the normal aging process has added a new dimension to
these studies. In addition, the development of extraordinarily sensitive methods
of comparing the nucleotide sequences of DNA molecules has allowed this
maternally inherited mitochondrial genome to be used as in the fields of
metazoan evolution, archeology, history, and anthropology.
E. C. Slater
University of Southampton
United Kingdom
