Volume 7S (2007) AMSTERDAM • BOSTON • JENA • LONDON • NEW YORK • OXFORD • PARIS • PHILADELPHIA • SAN DIEGO • ST. LOUIS The official journal of the Mitochondria Research Society Affiliated with the Japanese Society of Mitochondrial Research and Medicine Editor-in-Chief: K.K. Singh, Mitochondrion Editorial Office, BLSC, L3-316, Department of Cancer Genetics, Roswell Park Cancer Institute, Elm and Carlton, Buffalo, NY 14263, USA. E-mail: [email protected] Honorary Editors: B. Chance, Philadelphia, PA, USA R. Luft, Stockholm, Sweden A.W. Linnane, Melbourne, Australia P.P. Slonimski, Gif sur Yvette, France Associate Editors: G. Attardi, Pasadena, CA, USA H.J. Majima, Kagoshima, Japan R.A. Butow, Dallas, TX, USA J.A. Morgan-Hughes, London, UK D. Clayton, Stanford, CA, USA R. Naviaux, San Diego, CA, USA K.J.A. Davies, Los Angeles, CA, USA S. Ohta, Kanagawa, Japan A.D.N.J. de Grey, Cambridge, UK J. Reed, La Jolla, CA, USA L. Grivell, Amsterdam, The Netherlands I. Reynolds, Pittsburgh, PA, USA Y. Goto, Tokyo, Japan M. Tanaka, Tokyo, Japan O. Hurko, Collegeville, PA, USA A.A. Tzagoloff, New York, NY, USA N. Ishii, Kanagawa, Japan D. Wallace, Irvine, CA, USA R. Jansen, Sydney, Australia D.R. Wolstenhome, Salt Lake City, UT, USA G. Kroemer, Villejuif, France S. Zullo, Gaithersburg, MD, USA K. Kita, Tokyo, Japan Assistant Editors: V. Bohr, Baltimore, MD, USA C. Moraes, Miami, FL, USA G. Clark-Walker, Canberra, Australia P. Nagley, Clayton, Australia G. Cortopassi, Davis, CA, USA A.-L. Neiminen, Cleveland, OH, USA G. Fiskum, Baltimore, MD, USA G. Paradies, Bari, Italy M. Gerschenson, Honolulu, HI, USA P. Pedersen, Baltimore, MD, USA G. Gibson, White Plains, NY, USA G. Singh, Hamilton, Canada L. Grossman, Detroit, MI, USA V. Sukhorukov, Moscow, Russia M. Hanson, Ithaca, NY, USA M. Trush, Baltimore, MD, USA R.E. Jensen, Baltimore, MD, USA B. Van Houten, Research Triangle Park, NC, USA R. Kelley, Baltimore, MD, USA T. Wakabayashi, Gdansk, Poland A.S. Lewin, Gainesville, FL, USA K. Wallace, Duluth, MN, USA M.W. McEnery, Cleveland, OH, USA M. Yaffe, La Jolla, CA, USA Volume 7S (2007) AMSTERDAM • BOSTON • JENA • LONDON • NEW YORK • OXFORD • PARIS • PHILADELPHIA • SAN DIEGO • ST. LOUIS Ó 2007 Elsevier B.V. and Mitochondria Research Society. All rights reserved. This journal and the individual contributions contained in it are protected under copyright by Elsevier B.V., and the following terms and conditions apply to their use: Photocopying Single photocopies of single articles may be made for personal use as allowed by national copyright laws. Permission of the Publisher and payment of a fee is required for all other photocopying, including multiple or systematic copying, copying for advertising or promotional purposes, resale, and all forms of document delivery. Special rates are available for educational institutions that wish to make photocopies for non-profit educational classroom use. 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Because of rapid advances in the medical sciences, in particular, independent verification of diagnoses and drug dosages should be made. Although all advertising material is expected to conform to ethical (medical) standards, inclusion in this publication does not constitute a guarantee or endorsement of the quality or value of such product or of the claims made of it by its manufacturer. The paper used in this publication meets the requirements of ANSI/NISO Z39.48-1992 (Permanence of Paper) Printed by Alden Group Ltd., Oxford, UK Supplement to Volume 7 The Role of Coenzyme Q in Cellular Metabolism: Current Biological and Clinical Aspects Guest Editor Richard H. Haas Vol. 7S June 2007 CONTENTS Abstracting/Indexing: BIOBASE; CAS; EMBASE; ISIÒ Current Contents Clinical Medicine; Research Alert; Science Citation Index – Expanded Special Issue: The Role of Coenzyme Q in Cellular Metabolism: Current Biological and Clinical Aspects Guest Editor: Richard H. Haas Foreword R.H. Haas (USA) S1 Discovery of ubiquinone (coenzyme Q) and an overview of function F.L. Crane (USA) S2 The role of Coenzyme Q in mitochondrial electron transport G. Lenaz, R. Fato, G. Formiggini, M.L. Genova (Italy) S8 The importance of plasma membrane coenzyme Q in aging and stress responses P. Navas, J.M. Villalba (Spain), R. de Cabo (USA) S34 The antioxidant role of coenzyme Q M. Bentinger, K. Brismar, G. Dallner (Sweden) S41 Coenzyme Q10 – Its role as a prooxidant in the formation of superoxide anion/hydrogen peroxide and the regulation of the metabolome A.W. Linnane, M. Kios, L. Vitetta (Australia) S51 Endogenous synthesis of coenzyme Q in eukaryotes U.C. Tran, C.F. Clarke (USA) S62 The uptake and distribution of coenzyme Q(10) M.V. Miles (USA) S72 Plasma coenzyme Q10 response to oral ingestion of coenzyme Q10 formulations H.N. Bhagavan, R.K. Chopra (USA) S78 Analysis of coenzyme Q in human blood and tissues B.A. Barshop, J.A. Gangoiti (USA) S89 Mitochondrial targeting of quinones: Therapeutic implications H.M. Cocheme´ (UK), G.F. Kelso (New Zealand), A.M. James, M.F. Ross, J. Trnka, T. Mahendiran, J. Asin-Cayuela (UK), F.H. Blaikie, A.B. Manas, C.M. Porteous, V.J. Adlam, R.A.J. Smith (New Zealand), M.P. Murphy (UK) S94 Coenzyme Q, oxidative stress and aging R.S. Sohal, M.J. Forster (USA) S103 Infantile and pediatric quinone deficiency diseases A. Ro¨tig, J. Mollet, M. Rio, A. Munnich (France) S112 CoQ10 deficiency diseases in adults C.M. Quinzii, M. Hirano, S. DiMauro (USA) S122 FriedreichÕs ataxia: Coenzyme Q10 and vitamin E therapy J.M. Cooper, A.H.V. Schapira (UK) S127 The evidence basis for coenzyme Q therapy in oxidative phosphorylation disease R.H. Haas (USA) S136 Coenzyme Q treatment of neurodegenerative diseases of aging W.R. Galpern, M.E. Cudkowicz (USA) S146 Coenzyme Q10 in cardiovascular disease S. Pepe, S.F. Marasco, S.J. Haas, F.L. Sheeran, H. Krum, F.L. Rosenfeldt (Australia) S154 Coenzyme Q10 and statins: Biochemical and clinical implications G.P. Littarru (Italy), P. Langsjoen (USA) S168 Coenzyme Q10 in phenylketonuria and mevalonic aciduria I.P. Hargreaves (UK) S175 Calendar of Events I Mitochondrion 7S (2007) S1 www.elsevier.com/locate/mito Foreword This special edition of ‘Mitochondrion’ has provided a Novel designer quinone derivatives targeted to the mito- unique opportunity to gather together many of the chondrion are discussed as promising therapeutic agents. world’s experts on Coenzyme Q who have graciously The therapeutic role is further explored with practical provided timely reviews of their respective areas of re- information on pharmacokinetics, bioavailability and as- search expertise. I am particularly indebted to Professors say methodologies moving on to disease descriptions and Frederick Crane and Anthony Linnane for their support, the evidence for treatment efficacy in the rare genetic dis- helpful advice on the composition of this edition and for orders of primary Coenzyme Q10 deficiency, Friedreich’s providing excellent manuscripts of their own. Professor ataxia, mitochondrial disease, phenylketonuria and the Crane’s article is appropriately the first in this collection common neurodegenerative disorders of aging. A discus- as he is the discoverer of ubiquinone. He provides an sion of the evidence supporting the use of supplementa- invaluable historical perspective along with an overview tion in cardiovascular disease is complimented by an of the current state of research. Professor Linnane adds overview of statin drug effects on the mevalonic pathway a cautionary note pointing out that the pro-oxidant and Coenzyme Q10 synthesis. and signaling role of Coenzyme Q is critical for an array This edition would not have been possible without the ra- of cellular functions and should not be overlooked in the pid and thoughtful review of these contributions by expert current focus on antioxidant function and high dose reviewers from around the world to whom I owe a particular treatment. debt of gratitude. The goal of this edition is to provide a The timing of this special edition is opportune. Large state of the art comprehensive review of a unique molecule scale phase 3 clinical trials of high dose Coenzyme Q10 in which as its original name ubiquinone implies is found neurodegenerative disease are about to start and just in ubiquitously throughout the cell.