Mitochondrial ROS Metabolism: 10 Years Later

Abstract

The role of mitochondria in oxidative stress is well recognized, but many questions are still to be answered. This article is intended to update our comprehensive review in 2005 by highlighting the progress in understanding of mitochondrial reactive oxygen species (ROS) metabolism over the past 10 years. We review the recently identified or re-appraised sources of ROS generation in mitochondria, such as p66(shc) protein, succinate dehydrogenase, and recently discovered properties of the mitochondrial antioxidant system. We also reflect upon some controversies, disputes, and misconceptions that confound the field.

Fig. 1

General scheme of the respiratory chain with the sites of inhibitors of electron transfer. IM, inner mitochondrial membrane; R.e.T., reverse electron transport; F.e.T., forward electron transport; C I(III), Complex I(III) of mitochondrial respiratory chain; SDH, succinate dehydrogenase; ETF, electron-transferring flavoprotein; ETFQ, electron transfer flavoprotein:quinone oxidoreductase; CO, cytochrome c oxidase; Cyt c, cytochrome c; DHO DH, dihydroorotate dehydrogenase; α-GDH, α-glycerophosphate dehydrogenase; TTFA, thenoyltrifluoroacetone; FA, fatty acids.

Fig. 2

Mitochondrial ROS removal system. a) General scheme of enzymatic mitochondrial ROS removal system. b) Contribution of individual enzymes to ROS removal. See text for details. MnSOD, manganese-containing superoxide dismutase 2 (SOD2); Prx3, peroxiredoxin 3; Prx5, peroxiredoxin 5; GPx1, glutathione peroxidase 1; GSH, glutathione; GSSG, glutathione disulfide (oxidized glutathione); Trx2-red, thioredoxin 2, reduced; Trx2-ox, thioredoxin 2, oxidized; TrxR2, thioredoxin reductase 2; TH, transhydrogenase; GR, glutathione reductase; ME, malic enzyme; IDH, isocitrate dehydrogenase, NADP⁺-linked; ΔΨ, membrane potential. For the characteristics of individual enzymes and more details, see [6, 15, 74].