PGC-1α/ERRα-Sirt3 Pathway Regulates DAergic Neuronal Death by Directly Deacetylating SOD2 and ATP Synthase β.

ABSTRACT:

Aims

Parkinson's disease (PD) heavily affects humans and little is known about its cause and pathogenesis. Sirtuin 3 (Sirt3) plays a key role in regulating mitochondrial dysfunction, which is the main cause of DAergic neuronal loss in PD. We investigated the mechanisms of neuroprotective role of Sirt3 in DAergic neuronal survival.

Results

Sirt3 was reduced in 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine (MPTP)-treated neurons with its overexpression being neuroprotective. We identified that Sirt3 interacted with manganese superoxide dismutase (SOD2) and adenosine triphosphate (ATP) synthase β and modulated their activities by deacetylating SOD2 (K130) and ATP synthase β (K485) to prevent reactive oxygen species accumulation and ATP depletion, and to alleviate DAergic neurona

SUBMITTER: Zhang X 

PROVIDER: S-EPMC4761832 | biostudies-literature | 2016 Feb

REPOSITORIES: biostudies-literature