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An Update on Mitochondrial Reactive Oxygen Species Production

The School of Human Nutrition, Faculty of Agricultural and Environmental Sciences, McGill University, 21111 Lakeshore Road, Sainte-Anne-de-Bellevue, QC H9X 3V9, Canada
Antioxidants 2020, 9(6), 472;
Received: 20 April 2020 / Revised: 27 May 2020 / Accepted: 29 May 2020 / Published: 2 June 2020
(This article belongs to the Special Issue Redox and Nitrosative Signaling and Stress)
Mitochondria are quantifiably the most important sources of superoxide (O2●−) and hydrogen peroxide (H2O2) in mammalian cells. The overproduction of these molecules has been studied mostly in the contexts of the pathogenesis of human diseases and aging. However, controlled bursts in mitochondrial ROS production, most notably H2O2, also plays a vital role in the transmission of cellular information. Striking a balance between utilizing H2O2 in second messaging whilst avoiding its deleterious effects requires the use of sophisticated feedback control and H2O2 degrading mechanisms. Mitochondria are enriched with H2O2 degrading enzymes to desensitize redox signals. These organelles also use a series of negative feedback loops, such as proton leaks or protein S-glutathionylation, to inhibit H2O2 production. Understanding how mitochondria produce ROS is also important for comprehending how these organelles use H2O2 in eustress signaling. Indeed, twelve different enzymes associated with nutrient metabolism and oxidative phosphorylation (OXPHOS) can serve as important ROS sources. This includes several flavoproteins and respiratory complexes I-III. Progress in understanding how mitochondria generate H2O2 for signaling must also account for critical physiological factors that strongly influence ROS production, such as sex differences and genetic variances in genes encoding antioxidants and proteins involved in mitochondrial bioenergetics. In the present review, I provide an updated view on how mitochondria budget cellular H2O2 production. These discussions will focus on the potential addition of two acyl-CoA dehydrogenases to the list of ROS generators and the impact of important phenotypic and physiological factors such as tissue type, mouse strain, and sex on production by these individual sites. View Full-Text
Keywords: mitochondria; reactive oxygen species; bioenergetics; hydrogen peroxide; sex differences; substrate preferences; isopotential groups mitochondria; reactive oxygen species; bioenergetics; hydrogen peroxide; sex differences; substrate preferences; isopotential groups
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Mailloux, R.J. An Update on Mitochondrial Reactive Oxygen Species Production. Antioxidants 2020, 9, 472.

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