Perturbed Redox Signaling Exacerbates a Mitochondrial Myopathy

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Dogan , S A , Cerutti , R , Benincá , C , Brea-Calvo , G , Jacobs , H T , Zeviani , M , Szibor , M & Viscomi , C 2018 , ' Perturbed Redox Signaling Exacerbates a Mitochondrial Myopathy ' , Cell Metabolism , vol. 28 , no. 5 , pp. 764-+ .

Title: Perturbed Redox Signaling Exacerbates a Mitochondrial Myopathy
Author: Dogan, Sukru Anil; Cerutti, Raffaele; Benincá, Cristiane; Brea-Calvo, Gloria; Jacobs, Howard Trevor; Zeviani, Massimo; Szibor, Marten; Viscomi, Carlo
Contributor organization: Institute of Biotechnology
Date: 2018-11-06
Language: eng
Number of pages: 17
Belongs to series: Cell Metabolism
ISSN: 1550-4131
Abstract: Summary Alternative oxidases (AOXs) bypass respiratory complexes III and IV by transferring electrons from coenzyme Q directly to O2. They have therefore been proposed as a potential therapeutic tool for mitochondrial diseases. We crossed the severely myopathic skeletal muscle-specific COX15 knockout (KO) mouse with an AOX-transgenic mouse. Surprisingly, the double KO-AOX mutants had decreased lifespan and a substantial worsening of the myopathy compared with KO alone. Decreased ROS production in KO-AOX versus KO mice led to impaired AMPK/PGC-1α signaling and PAX7/MYOD-dependent muscle regeneration, blunting compensatory responses. Importantly, the antioxidant N-acetylcysteine had a similar effect, decreasing the lifespan of KO mice. Our findings have major implications for understanding pathogenic mechanisms in mitochondrial diseases and for the design of therapies, highlighting the benefits of ROS signaling and the potential hazards of antioxidant treatment.
Subject: mitochondrial biogenesis
alternative oxidase
redox signaling
mitochondrial disease
stress responses
satellite cells
1182 Biochemistry, cell and molecular biology
Peer reviewed: Yes
Rights: cc_by
Usage restriction: openAccess
Self-archived version: draft

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