Blocking Reactive Oxygen Species Generation Inhibits Biogenesis in Mitochondrial Dysfunction
While until recently reactive oxygen species (ROS) were thought to mainly act as agents of cell damage, there is growing information on the role of ROS as mediators of signaling to regulate cellular homeostasis. In an article published in Cell Metabolism (2018 November 28; 6:764–775. doi: 10.1016/j.cmet.2018.07.012), Dogan and colleagues reported a notable decline of the clinical and biochemical phenotype in a double mutant model of cytochromec oxidase-defective mitochondrial myopathy and alternative oxidase (AOX). AOX directly oxidizes ubiquinone, preserving electron flow from carriers NADH and FADH2, and abolishes the contribution of complexes III and IV to membrane potential in the mitochondrial respiratory chain. Although AOX can limit the generation of ROS and preserve redox homeostasis, thereby maintaining tricarboxylic acid cycle activity, the authors highlight that antioxidants can inhibit the homeostatic response to bioenergetic failure by modulating mitochondrial biogenesis. The result supports that interruption of ROS signaling might negatively impact the induction of mitochondrial biogenesis and antioxidant gene expression. This prevents cellular processes that are subject to redox regulation for oxidative damage chain, thereby leading to mitochondrial dysfunction.
Submission of an original manuscript to the Journal will be taken to mean that it represents original work not previously published; that it is not being considered elsewhere for publication; that the author(s) agrees to assign copyright to the Journal upon acceptance for publication in the Journal, and if accepted for publication, it will be published in the digital format (PDF) and/or in print and it will not be published elsewhere in the same form, for commercial purposes, in any language, without the consent of the Publisher.