title: Mitochondria: Inadvertent targets in chemotherapy-induced skeletal muscle toxicity and wasting?
abstract: Chemotherapy has been associated with increased mitochondrial reactive oxygen species production, mitochondrial dysfunction and skeletal muscle atrophy leading to severe patient clinical complications including skeletal muscle fatigue, insulin resistance and wasting. The exact mechanisms behind this skeletal muscle toxicity are largely unknown, and as such co-therapies to attenuate chemotherapy-induced side effects are lacking. Here, we review the current literature describing the clinical manifestations and molecular origins of chemotherapy-induced myopathy with a focus on the mitochondria as the target organelle via which chemotherapeutic agents establish toxicity. We explore the likely mechanisms through which myopathy is induced, using the anthracycline doxorubicin, and the platinum-based alkylating agent oxaliplatin, as examples. Finally, we recommend directions for future research and outline the potential significance of these proposed directions.
authors.affiliation: Centre for Chronic Disease, College of Health and Biomedicine, Victoria University, Melbourne, 8001, Australia.|Australian Institute of Musculoskeletal Science, Western Health, Melbourne, 3021, Australia.
authors.forename: James C
authors.initials: JC
authors.lastname: Sorensen
authors.affiliation: Centre for Chronic Disease, College of Health and Biomedicine, Victoria University, Melbourne, 8001, Australia.
authors.forename: Beatrice D
authors.initials: BD
authors.lastname: Cheregi
authors.affiliation: Centre for Chronic Disease, College of Health and Biomedicine, Victoria University, Melbourne, 8001, Australia.|Australian Institute of Musculoskeletal Science, Western Health, Melbourne, 3021, Australia.
authors.forename: Cara A
authors.initials: CA
authors.lastname: Timpani
authors.affiliation: Centre for Chronic Disease, College of Health and Biomedicine, Victoria University, Melbourne, 8001, Australia.
authors.forename: Kulmira
authors.initials: K
authors.lastname: Nurgali
authors.affiliation: Centre for Chronic Disease, College of Health and Biomedicine, Victoria University, Melbourne, 8001, Australia.|Institute of Sport, Exercise and Active Living (ISEAL), Victoria University, Melbourne, 8001, Australia.|Australian Institute of Musculoskeletal Science, Western Health, Melbourne, 3021, Australia.
authors.forename: Alan
authors.initials: A
authors.lastname: Hayes
authors.affiliation: Centre for Chronic Disease, College of Health and Biomedicine, Victoria University, Melbourne, 8001, Australia. emma.rybalka@vu.edu.au.|Institute of Sport, Exercise and Active Living (ISEAL), Victoria University, Melbourne, 8001, Australia. emma.rybalka@vu.edu.au.|Australian Institute of Musculoskeletal Science, Western Health, Melbourne, 3021, Australia. emma.rybalka@vu.edu.au.
authors.forename: Emma
authors.initials: E
authors.lastname: Rybalka
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D006801:Humans; D008931:Mitochondria, Muscle / Q000187:drug effects* / Q000473:pathology; D017240:Mitochondrial Myopathies / Q000139:chemically induced* / Q000473:pathology; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000473:pathology; D009135:Muscular Diseases / Q000139:chemically induced* / Q000473:pathology; D019282:Wasting Syndrome / Q000139:chemically induced* / Q000473:pathology
chemical_list: D000970:Antineoplastic Agents
keywords: Anti-cancer chemotherapy; Mitochondria; Skeletal muscle; Toxicity