Pieter A Leermakers1, Harry R Gosker. 1. Department of Respiratory Medicine, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Centre+, Maastricht, The Netherlands.
Abstract
PURPOSE OF REVIEW: Loss of skeletal muscle oxidative capacity is a common feature of chronic diseases such as chronic obstructive pulmonary disease, type 2 diabetes, and congestive heart failure. It may lead to physical impairments and has been suggested to contribute to metabolic inflexibility-induced cardiometabolic risk. The mechanism underlying loss of muscle oxidative capacity is incompletely understood. This review discusses the role of mitophagy as a driving force behind the loss of skeletal muscle oxidative capacity in these patients. RECENT FINDINGS: Mitophagy has been studied to a very limited extent in human skeletal muscle. There are, however, clear indications that disease-related factors, including hypoxia, systemic inflammation, muscle inactivity, and iron deficiency are able to induce mitophagy, and that these factors trigger mitophagy via different regulatory mechanisms. Although mitophagy may lead to mitochondrial loss, it is also required to maintain homeostasis through clearance of damaged mitochondria. SUMMARY: Based on available evidence, we propose that enhanced mitophagy is involved in chronic disease-induced loss of muscle oxidative capacity. Clearly more research is required to confirm this role and to establish to what extent mitophagy is pathological or a part of physiological adaptation to maintain muscle health.
PURPOSE OF REVIEW: Loss of skeletal muscle oxidative capacity is a common feature of chronic diseases such as chronic obstructive pulmonary disease, type 2 diabetes, and congestive heart failure. It may lead to physical impairments and has been suggested to contribute to metabolic inflexibility-induced cardiometabolic risk. The mechanism underlying loss of muscle oxidative capacity is incompletely understood. This review discusses the role of mitophagy as a driving force behind the loss of skeletal muscle oxidative capacity in these patients. RECENT FINDINGS: Mitophagy has been studied to a very limited extent in human skeletal muscle. There are, however, clear indications that disease-related factors, including hypoxia, systemic inflammation, muscle inactivity, and iron deficiency are able to induce mitophagy, and that these factors trigger mitophagy via different regulatory mechanisms. Although mitophagy may lead to mitochondrial loss, it is also required to maintain homeostasis through clearance of damaged mitochondria. SUMMARY: Based on available evidence, we propose that enhanced mitophagy is involved in chronic disease-induced loss of muscle oxidative capacity. Clearly more research is required to confirm this role and to establish to what extent mitophagy is pathological or a part of physiological adaptation to maintain muscle health.
Authors: Gourav Bhardwaj; Christie M Penniman; Jayashree Jena; Pablo A Suarez Beltran; Collin Foster; Kennedy Poro; Taylor L Junck; Antentor O Hinton; Rhonda Souvenir; Jordan D Fuqua; Pablo E Morales; Roberto Bravo-Sagua; William I Sivitz; Vitor A Lira; E Dale Abel; Brian T O'Neill Journal: J Clin Invest Date: 2021-09-15 Impact factor: 14.808
Authors: P A Leermakers; A M W J Schols; A E M Kneppers; M C J M Kelders; C C de Theije; M Lainscak; H R Gosker Journal: Sci Rep Date: 2018-10-09 Impact factor: 4.379
Authors: Pieter A Leermakers; Anita E M Kneppers; Annemie M W J Schols; Marco C J M Kelders; Chiel C de Theije; Lex B Verdijk; Luc J C van Loon; Ramon C J Langen; Harry R Gosker Journal: Muscle Nerve Date: 2019-10-23 Impact factor: 3.217