Uremic metabolites impair skeletal muscle mitochondrial energetics through disruption of the electron transport system and matrix dehydrogenase activity.

ABSTRACT: Chronic kidney disease (CKD) leads to increased skeletal muscle fatigue, weakness, and atrophy. Previous work has implicated mitochondria within the skeletal muscle as a mediator of muscle dysfunction in CKD; however, the mechanisms underlying mitochondrial dysfunction in CKD are not entirely known. The purpose of this study was to define the impact of uremic metabolites on mitochondrial energetics. Skeletal muscle mitochondria were isolated from C57BL/6N mice and exposed to vehicle (DMSO) or varying concentrations of uremic metabolites: indoxyl sulfate, indole-3-acetic-acid, l-kynurenine, and kynurenic acid. A comprehensive mitochondrial phenotyping platform that included assessments of mitochondrial oxidative phosphorylation (OXPHOS) conductance and respiratory capacity, hydrogen peroxid

SUBMITTER: Thome T 

PROVIDER: S-EPMC6851000 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature