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Therefore, preventive measures are of primary importance; however, little is known about muscle perturbations prior to onset of cachexia. Cancer cachexia is associated with mitochondrial degeneration; yet, it remains to be determined if mitochondrial degeneration precedes muscle wasting in cancer cachexia. Therefore, our purpose was to determine if mitochondrial degeneration precedes cancer\u2010induced muscle wasting in tumour\u2010bearing mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>First, weight\u2010stable (MinStable) and cachectic (MinCC) <jats:italic>Apc<\/jats:italic><jats:sup><jats:italic>Min\/+<\/jats:italic><\/jats:sup> mice were compared with C57Bl6\/J controls for mRNA contents of mitochondrial quality regulators in quadriceps muscle. Next, Lewis lung carcinoma (LLC) cells or PBS (control) were injected into the hind flank of C57Bl6\/J mice at 8\u00a0week age, and tumour allowed to develop for 1, 2, 3, or 4\u00a0weeks to examine time course of cachectic development. Succinate dehydrogenase stain was used to measure oxidative phenotype in tibialis anterior muscle. Mitochondrial quality and function were assessed using the reporter MitoTimer by transfection to flexor digitorum brevis and mitochondrial function\/ROS emission in permeabilized adult myofibres from plantaris. RT\u2010qPCR and immunoblot measured the expression of mitochondrial quality control and antioxidant proteins. Data were analysed by one\u2010way ANOVA with Student\u2013Newman\u2013Kuels post hoc test.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>MinStable mice displayed ~50% lower <jats:italic>Pgc\u20101\u03b1<\/jats:italic>, <jats:italic>Ppar\u03b1<\/jats:italic>, and <jats:italic>Mfn2<\/jats:italic> compared with C57Bl6\/J controls, whereas MinCC exhibited 10\u2010fold greater <jats:italic>Bnip3<\/jats:italic> content compared with C57Bl6\/J controls. In LLC, cachectic muscle loss was evident only at 4\u00a0weeks post\u2010tumour implantation. Oxidative capacity and mitochondrial content decreased by ~40% 4\u00a0weeks post\u2010tumour implantation. Mitochondrial function decreased by ~25% by 3\u00a0weeks after tumour implantation. Mitochondrial degeneration was evident by 2\u00a0week LLC compared with PBS control, indicated by MitoTimer red\/green ratio and number of pure red puncta. Mitochondrial ROS production was elevated by ~50 to ~100% when compared with PBS at 1\u20133\u00a0weeks post\u2010tumour implantation. Mitochondrial quality control was dysregulated throughout the progression of cancer cachexia in tumour\u2010bearing mice. In contrast, antioxidant proteins were not altered in cachectic muscle wasting.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Functional mitochondrial degeneration is evident in LLC tumour\u2010bearing mice prior to muscle atrophy. Contents of mitochondrial quality regulators across <jats:italic>Apc<\/jats:italic><jats:sup><jats:italic>Min\/+<\/jats:italic><\/jats:sup> and LLC mice suggest impaired mitochondrial quality control as a commonality among pre\u2010clinical models of cancer cachexia. Our data provide novel evidence for impaired mitochondrial health prior to cachectic muscle loss and provide a potential therapeutic target to prevent cancer cachexia.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jcsm.12232","type":"journal-article","created":{"date-parts":[[2017,8,28]],"date-time":"2017-08-28T08:12:41Z","timestamp":1503907961000},"page":"926-938","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":281,"title":["Mitochondrial degeneration precedes the development of muscle atrophy in progression of cancer cachexia in tumour\u2010bearing mice"],"prefix":"10.1002","volume":"8","author":[{"given":"Jacob L.","family":"Brown","sequence":"first","affiliation":[{"name":"Integrative Muscle Metabolism Laboratory, Exercise Science Research Center, Department of Health, Human Performance and Recreation University of Arkansas  Fayetteville AR 72701 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megan 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A.","family":"Brown","sequence":"additional","affiliation":[{"name":"Exercise Muscle Biology Laboratory, Exercise Science Research Center, Department of Health, Human Performance and Recreation University of Arkansas  Fayetteville AR 72701 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard A.","family":"Perry","sequence":"additional","affiliation":[{"name":"Exercise Muscle Biology Laboratory, Exercise Science Research Center, Department of Health, Human Performance and Recreation University of Arkansas  Fayetteville AR 72701 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wesley S.","family":"Haynie","sequence":"additional","affiliation":[{"name":"Exercise Muscle Biology Laboratory, Exercise Science Research Center, Department of Health, Human Performance and Recreation University of Arkansas  Fayetteville AR 72701 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justin 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