MicroRNA-181a suppresses parkin-mediated mitophagy and sensitizes neuroblastoma cells to mitochondrial uncoupler-induced apoptosis.

ABSTRACT: Damage to mitochondria often results in the activation of both mitophagy and mitochondrial apoptosis. The elimination of dysfunctional mitochondria is necessary for mitochondrial quality maintenance and efficient energy supply. Here we report that miR-181a is a novel inhibitor of mitophagy. miR-181a is downregulated by mitochondrial uncouplers in human neuroblastoma SH-SY5Y cells. Overexpression of miR-181a inhibits mitochondrial uncoupling agents-induced mitophagy by inhibiting the degradation of mitochondrial proteins without affecting global autophagy. Knock down of endogenous miR-181a accelerates the autophagic degradation of damaged mitochondria. miR-181a directly targets Parkin E3 ubiquitin ligase and partially blocks the colocalization of mitochondria and autophagosomes/lysosomes. R

SUBMITTER: Cheng M 

PROVIDER: S-EPMC5173134 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature