δ-opioid receptor activation protects against Parkinson's disease-related mitochondrial dysfunction by enhancing PINK1/Parkin-dependent mitophagy.

ABSTRACT: Our previous studies have shown that the δ-opioid receptor (DOR) is an important neuroprotector via the regulation of PTEN-induced kinase 1 (PINK1), a mitochondria-related molecule, under hypoxic and MPP⁺ insults. Since mitochondrial dysfunctions are observed in both hypoxia and MPP⁺ insults, this study further investigated whether DOR is cytoprotective against these insults by targeting mitochondria. Through comparing DOR-induced responses to hypoxia versus MPP⁺-induced parkinsonian insult in PC12 cells, we found that both hypoxia and MPP⁺ caused a collapse of mitochondrial membrane potential and severe mitochondrial dysfunction. In sharp contrast to its inappreciable effect on mitochondria in hypoxic conditions, DOR activation with UFP-512, a s

SUBMITTER: Xu Y 

PROVIDER: S-EPMC7803568 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature