Mitochondrial carrier protein overloading and misfolding induce aggresomes and proteostatic adaptations in the cytosol.

ABSTRACT: Previous studies in yeast showed that mitochondrial stressors not directly targeting the protein import machinery can cause mitochondrial precursor overaccumulation stress (mPOS) in the cytosol independent of bioenergetics. Here, we demonstrate mPOS and stress responses in human cells. We show that overloading of mitochondrial membrane carrier, but not matrix proteins, is sufficient to induce cytosolic aggresomes and apoptosis. The aggresomes appear to triage unimported mitochondrial proteins. Interestingly, expression of highly unstable mutant variants of the mitochondrial carrier protein, Ant1, also induces aggresomes despite a greater than 20-fold reduction in protein level compared to wild type. Thus, overloading of the protein import machinery, rather than protein accumulation, is cri

SUBMITTER: Liu Y 

PROVIDER: S-EPMC6724602 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature