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

Abstract

In this minireview, 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 (Y302 in R. capsulatus and Y278 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.

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“…Complexes I and III are large responsible for superoxide anion radical generation (Lanciano et al., ; Markevich & Hoek, ). Superoxide anion radical generated are dismutated to H 2 O 2 , which undergoes Fenton reaction (in the presence of Fe 2+ ) to produce hydroxyl radical.…”

Global Protein Oxidation Profiling Suggests Efficient Mitochondrial Proteome Homeostasis During Aging

“…Mitochondria are known as the main source of endogenous ROS, mainly generated as by-products of oxidative phosphorylation (OXPHOS) at complexes I and III of the respiratory electron transport chain (3,4). Consequently, mitochondria are inevitably the most prominent target of ROSinduced damage (5).…”

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