title: Skeletal muscle mitophagy in chronic disease: implications for muscle oxidative capacity?
abstract: 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.
  
  
  
  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.
  
  
  
  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.affiliation: Department of Respiratory Medicine, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Centre+, Maastricht, The Netherlands.
authors.forename: Pieter A
authors.initials: PA
authors.lastname: Leermakers
authors.forename: Harry R
authors.initials: HR
authors.lastname: Gosker
mesh_terms: D000818:Animals; D002908:Chronic Disease; D003924:Diabetes Mellitus, Type 2; D006333:Heart Failure; D006706:Homeostasis; D006801:Humans; D000860:Hypoxia; D007249:Inflammation; D000090463:Iron Deficiencies; D008931:Mitochondria, Muscle / Q000502:physiology; D063306:Mitophagy / Q000502:physiology*; D018482:Muscle, Skeletal / Q000378:metabolism*; D010084:Oxidation-Reduction; D029424:Pulmonary Disease, Chronic Obstructive