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Molecular mechanisms of superoxide production by complex III: A bacterial versus human mitochondrial comparative case study

Lanciano, Pascal, Khalfaoui-Hassani, Bahia, Selamoglu, Nur, Ghelli, Anna, Rugolo, Michela, Daldal, Fevzi
Biochimica et biophysica acta 2013 v.1827 no.11-12 pp. 1332-1339
Rhodobacter capsulatus, case studies, catalytic activity, cybrids, cytochrome b, electron transfer, humans, mitochondria, mutants, mutation, oxidation, protective effect, reactive oxygen species, tyrosine
In this mini review, we briefly survey the molecular processes that lead to reactive oxygen species (ROS) production by the respiratory complex III (CIII or cytochrome bc1). In particular, we discuss the “forward” and “reverse” electron transfer pathways that lead to superoxide generation at the quinol oxidation (Qo) site of CIII, and the components that affect these reactions. We then describe and compare the properties of a bacterial (Rhodobacter capsulatus) mutant enzyme producing ROS with its mitochondrial (human cybrids) counterpart associated with a disease. The mutation under study is located at a highly conserved tyrosine residue of cytochrome b (Y302C in R. capsulatus and Y278C in human mitochondria) that is at the heart of the quinol oxidation (Qo) site of CIII. Similarities of the major findings of bacterial and human mitochondrial cases, including decreased catalytic activity of CIII, enhanced ROS production and ensuing cellular responses and damages, are remarkable. This case illustrates the usefulness of undertaking parallel and complementary studies using biologically different yet evolutionarily related systems, such as α-proteobacteria and human mitochondria. It progresses our understanding of CIII mechanism of function and ROS production, and underlines the possible importance of supra-molecular organization of bacterial and mitochondrial respiratory chains (i.e., respirasomes) and their potential disease-associated protective roles. This article is part of a Special Issue entitled: Respiratory complex III and related bc complexes.