PINK1 phosphorylates Drp1^S616 to regulate mitophagy-independent mitochondrial dynamics.

ABSTRACT: Impairment of PINK1/parkin-mediated mitophagy is currently proposed to be the molecular basis of mitochondrial abnormality in Parkinson's disease (PD). We here demonstrate that PINK1 directly phosphorylates Drp1 on S616. Drp1^S616 phosphorylation is significantly reduced in cells and mouse tissues deficient for PINK1, but unaffected by parkin inactivation. PINK1-mediated mitochondrial fission is Drp1^S616 phosphorylation dependent. Overexpression of either wild-type Drp1 or of the phosphomimetic mutant Drp1^S616D , but not a dephosphorylation-mimic mutant Drp1^S616A , rescues PINK1 deficiency-associated phenotypes in Drosophila. Moreover, Drp1 restores PINK1-dependent mitochondrial fission in ATG5-null cells and ATG7-null Drosophila. Reduced Drp1

SUBMITTER: Han H 

PROVIDER: S-EPMC7403662 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature