Dissociation of superoxide production by mitochondrial complex I from NAD(P)H redox state

被引：29

作者：

Lambert, Adrian J. ^{[1
]}

Buckingham, Julie A. ^{[1
]}

Brand, Martin D. ^{[1
]}

机构：

[1] MRC, Dunn Human Nutr Unit, Cambridge CB2 0XY, England

来源：

FEBS LETTERS | 2008年 / 582卷 / 12期

基金：

英国医学研究理事会; 英国惠康基金;

关键词：

NADH : ubiquinone oxidoreductase; mitochondria; superoxide; NAD(P)H; hydrogen peroxide; reactive oxygen species;

D O I：

10.1016/j.febslet.2008.04.030

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The relationship between the rate of superoxide production by complex I and NAD(P) H redox state was investigated in rat skeletal muscle mitochondria. A high rate of superoxide production was observed during succinate oxidation; the rate during pyruvate oxidation was over fourfold lower. However, the NAD(P) H pool was significantly less reduced during succinate oxidation than during pyruvate oxidation. We conclude that there is no unique relationship between superoxide production by complex I and the reduction state of the NAD(P) H pool. Our data suggest that less than 10% of the superoxide originates from the flavin site during reverse electron transport from succinate. (C) 2008 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

引用

页码：1711 / 1714

页数：4

共 21 条

[1] Mitochondrial superoxide: Production, biological effects, and activation of uncoupling proteins [J].

Brand, MD ;

Affourtit, C ;

Esteves, TC ;

Green, K ;

Lambert, AJ ;

Miwa, S ;

Pakay, JL ;

Parker, N .

FREE RADICAL BIOLOGY AND MEDICINE, 2004, 37 (06) :755-767

[2] Superoxide radical formation by pure complex I (NADH:Ubiquinone oxidoreductase) from Yarrowia lipolytica [J].

Galkin, A ;

Brandt, U .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2005, 280 (34) :30129-30135

[3] The site of production of superoxide radical in mitochondrial Complex I is not a bound ubisemiquinone but presumably iron-sulfur cluster N2 [J].

Genova, ML ;

Ventura, B ;

Giuliano, G ;

Bovina, C ;

Formiggini, G ;

Castelli, GP ;

Lenaz, G .

FEBS LETTERS, 2001, 505 (03) :364-368

[4] Dependence of H2O2 formation by rat heart mitochondria on substrate availability and donor age [J].

Hansford, RG ;

Hogue, BA ;

Mildaziene, V .

JOURNAL OF BIOENERGETICS AND BIOMEMBRANES, 1997, 29 (01) :89-95

[5] RESPIRATORY CONTROL IN THE GLUCOSE PERFUSED HEART - A P-31 NMR AND NADH FLUORESCENCE STUDY [J].

KATZ, LA ;

KORETSKY, AP ;

BALABAN, RS .

FEBS LETTERS, 1987, 221 (02) :270-276

[6] Characterization of superoxide-producing sites in isolated brain mitochondria [J].

Kudin, AP ;

Bimpong-Buta, NYB ;

Vielhaber, S ;

Elger, CE ;

Kunz, WS .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2004, 279 (06) :4127-4135

[7] Complex I-mediated reactive oxygen species generation:: modulation by cytochrome c and NAD(P)+ oxidation-reduction state [J].

Kushnareva, Y ;

Murphy, AN ;

Andreyev, A .

BIOCHEMICAL JOURNAL, 2002, 368 :545-553

[8] The mechanism of superoxide production by NADH:ubiquinone oxidoreductase (complex I) from bovine heart mitochondria [J].

Kussmaul, Lothar ;

Hirst, Judy .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2006, 103 (20) :7607-7612

[9] Inhibitors of the quinone-binding site allow rapid superoxide production from mitochondrial NADH:ubiquinone oxidoreductase (complex I) [J].

Lambert, AJ ;

Brand, MD .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2004, 279 (38) :39414-39420

[10] Superoxide production by NADH: ubiquinone oxidoreductase (complex I) depends on the pH gradient across the mitochondrial inner membrane [J].

Lambert, AJ ;

Brand, MD .

BIOCHEMICAL JOURNAL, 2004, 382 :511-517

← 1 2 3 →