SIRT4 interacts with OPA1 and regulates mitochondrial quality control and mitophagy.

ABSTRACT: The stress-responsive mitochondrial sirtuin SIRT4 controls cellular energy metabolism in a NAD⁺-dependent manner and is implicated in cellular senescence and aging. Here we reveal a novel function of SIRT4 in mitochondrial morphology/quality control and regulation of mitophagy. We report that moderate overexpression of SIRT4, but not its enzymatically inactive mutant H161Y, sensitized cells to mitochondrial stress. CCCP-triggered dissipation of the mitochondrial membrane potential resulted in increased mitochondrial ROS levels and autophagic flux, but surprisingly led to increased mitochondrial mass and decreased Parkin-regulated mitophagy. The anti-respiratory effect of elevated SIRT4 was accompanied by increased levels of the inner-membrane bound long form of the GTPase OPA1 (

SUBMITTER: Lang A 

PROVIDER: S-EPMC5680561 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature