Preventing excessive autophagy protects from the pathology of mtDNA mutations in Drosophila melanogaster.

ABSTRACT: Aberration of mitochondrial function is a shared feature of many human pathologies, characterised by changes in metabolic flux, cellular energetics, morphology, composition, and dynamics of the mitochondrial network. While some of these changes serve as compensatory mechanisms to maintain cellular homeostasis, their chronic activation can permanently affect cellular metabolism and signalling, ultimately impairing cell function. Here, we use a Drosophila melanogaster model expressing a proofreading-deficient mtDNA polymerase (POLγ^exo-) in a genetic screen to find genes that mitigate the harmful accumulation of mtDNA mutations. We identify critical pathways associated with nutrient sensing, insulin signalling, mitochondrial protein import, and autophagy that can rescue the lethal

SUBMITTER: El Fissi N 

PROVIDER: S-EPMC11666730 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature