Perturbed Redox Signaling Exacerbates a Mitochondrial Myopathy

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http://hdl.handle.net/10138/288729

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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-+ . https://doi.org/10.1016/j.cmet.2018.07.012

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: University of Helsinki, Institute of Biotechnology
University of Helsinki, Institute of Biotechnology
Date: 2018-11-06
Language: eng
Number of pages: 17
Belongs to series: Cell Metabolism
ISSN: 1550-4131
URI: http://hdl.handle.net/10138/288729
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
ROS
redox signaling
autophagy
mitochondrial disease
antioxidant
stress responses
satellite cells
1182 Biochemistry, cell and molecular biology
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