High fat diet ameliorates mitochondrial cardiomyopathy in CHCHD10 mutant mice

ABSTRACT: Mutations in CHCHD10, a mitochondrial protein with undefined functions, are associated with autosomal dominant mitochondrial diseases. Chchd10 knock-in mice harboring a heterozygous S55L mutation (equivalent to human pathogenic S59L) develop a fatal mitochondrial cardiomyopathy caused by CHCHD10 aggregation and proteotoxic mitochondrial integrated stress response (mtISR). In mutant hearts, mtISR is accompanied by a metabolic rewiring characterized by increased reliance on glycolysis rather than fatty acid oxidation. To counteract this metabolic rewiring, heterozygous S55L mice were subjected to chronic high fat diet (HFD) to decrease insulin sensitivity and glucose uptake and enhance fatty acid utilization in the heart. HFD ameliorated the ventricular dysfunction of mutant hearts and signi

SUBMITTER: Nneka Southwell 

PROVIDER: S-SCDT-10_1038-S44321-024-00067-5 | biostudies-other |

REPOSITORIES: biostudies-other