Mitochondrial mistranslation modulated by metabolic stress causes cardiovascular disease and reduced lifespan

Changes in the rate and fidelity of mitochondrial protein synthesis impact the metabolic and physiological roles of mitochondria. Here we explored how environmental stress in the form of a high-fat diet modulates mitochondrial translation and affects lifespan in mutant mice with error-prone or hyper-accurate mitochondrial ribosomes. Intriguingly, although both mutations are metabolically beneficial in reducing body weight, decreasing circulating insulin and increasing glucose tolerance during a high-fat diet, they manifest divergent (either deleterious or beneficial) outcomes in a tissue-specific manner.

Citation:
Richman TR, Ermer JA, Siira SJ, ..... Rossetti G, Baker J, Perks KL, Cserne Szappanos H, Viola HM, ........Rackham O, Filipovska A. Mitochondrial mistranslation modulated by metabolic stress causes cardiovascular disease and reduced lifespan. Aging Cell. 2021

Keywords:
Ageing; metabolism; mitochondria; protein synthesis

Abstract:
Changes in the rate and fidelity of mitochondrial protein synthesis impact the metabolic and physiological roles of mitochondria. Here we explored how environmental stress in the form of a high-fat diet modulates mitochondrial translation and affects lifespan in mutant mice with error-prone or hyper-accurate mitochondrial ribosomes. Intriguingly, although both mutations are metabolically beneficial in reducing body weight, decreasing circulating insulin and increasing glucose tolerance during a high-fat diet, they manifest divergent (either deleterious or beneficial) outcomes in a tissue-specific manner.