Impaired muscle mitochondrial energetics is associated with uremic metabolite accumulation in chronic kidney disease

• DOI: 10.1172/jci.insight.139826
• Publication Date: 2020-12-08T17:04:16Z
• Authors: Trace Thome; Ravi A. Kumar; Sarah K. Burke; Ram B. Khattri; Zachary R. Salyers; Rachel C. Kelley; Madeline D. Coleman; Demetra D. Christou; Russell T. Hepple; Salvatore T. Scali; Leonardo F. Ferreira; Terence E. Ryan
• Keywords: Muscle Atrophy

Chronic kidney disease (CKD) causes progressive skeletal myopathy involving atrophy, weakness, and fatigue. Mitochondria have been thought to contribute myopathy; however, the molecular mechanisms underlying muscle metabolism changes in CKD are unknown. We employed a comprehensive mitochondrial phenotyping platform elucidate of impairment mice with adenine-induced CKD. displayed significant reductions oxidative phosphorylation (OXPHOS), which was strongly correlated glomerular filtration rate, suggesting link between function health. Biochemical assays uncovered that OXPHOS dysfunction driven by reduced activity matrix dehydrogenases. Untargeted metabolomics analyses revealed distinct metabolite profile including accumulation uremic toxins associated degree impairment. Additional found experienced atrophy increased protein degradation, but only male had lower maximal contractile force. morphological indicative destabilization neuromuscular junction. This study provides first evaluation health murine our knowledge uncovers several unknown metabolites associate