title: The emerging role of skeletal muscle oxidative metabolism as a biological target and cellular regulator of cancer-induced muscle wasting.
abstract: While skeletal muscle mass is an established primary outcome related to understanding cancer cachexia mechanisms, considerable gaps exist in our understanding of muscle biochemical and functional properties that have recognized roles in systemic health. Skeletal muscle quality is a classification beyond mass, and is aligned with muscle's metabolic capacity and substrate utilization flexibility. This supplies an additional role for the mitochondria in cancer-induced muscle wasting. While the historical assessment of mitochondria content and function during cancer-induced muscle loss was closely aligned with energy flux and wasting susceptibility, this understanding has expanded to link mitochondria dysfunction to cellular processes regulating myofiber wasting. The primary objective of this article is to highlight muscle mitochondria and oxidative metabolism as a biological target of cancer cachexia and also as a cellular regulator of cancer-induced muscle wasting. Initially, we examine the role of muscle metabolic phenotype and mitochondria content in cancer-induced wasting susceptibility. We then assess the evidence for cancer-induced regulation of skeletal muscle mitochondrial biogenesis, dynamics, mitophagy, and oxidative stress. In addition, we discuss environments associated with cancer cachexia that can impact the regulation of skeletal muscle oxidative metabolism. The article also examines the role of cytokine-mediated regulation of mitochondria function, followed by the potential role of cancer-induced hypogonadism. Lastly, a role for decreased muscle use in cancer-induced mitochondrial dysfunction is reviewed.
authors.affiliation: Integrative Muscle Biology Laboratory, Department of Exercise Science, University of South Carolina, 921 Assembly St., Columbia, SC, 29208, USA. Electronic address: carsonj@mailbox.sc.edu.
authors.forename: James A
authors.initials: JA
authors.lastname: Carson
authors.affiliation: Integrative Muscle Biology Laboratory, Department of Exercise Science, University of South Carolina, 921 Assembly St., Columbia, SC, 29208, USA.
authors.forename: Justin P
authors.initials: JP
authors.lastname: Hardee
authors.affiliation: Integrative Muscle Biology Laboratory, Department of Exercise Science, University of South Carolina, 921 Assembly St., Columbia, SC, 29208, USA.
authors.forename: Brandon N
authors.initials: BN
authors.lastname: VanderVeen
mesh_terms: D000818:Animals; D002100:Cachexia / Q000209:etiology* / Q000378:metabolism*; D006801:Humans; D008928:Mitochondria / Q000378:metabolism; D008954:Models, Biological; D018482:Muscle, Skeletal / Q000378:metabolism*; D009369:Neoplasms / Q000150:complications* / Q000378:metabolism*; D010084:Oxidation-Reduction
keywords: Cytokine; Disuse; Hypogonadism; Mitochondria