|Title:||Carnosic acid attenuated cytochrome c release through the mitochondrial structural protein Mic60 by PINK1 in SH-SY5Y cells||Authors:||Lin, Chia-Yuan
|Keywords:||Carnosic acid; Mic60; PINK1-mediated mitophagy; PKA; Parkinson's disease;Mic60;PINK1-mediated mitophagy;PKA;Parkinson's disease||Issue Date:||Mar-2023||Publisher:||PERGAMON-ELSEVIER SCIENCE||Journal Volume:||173||Source:||Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association||Abstract:||
Mitochondrial dysfunction has been implicated in Parkinson's disease. Mic60 is a critical component of mitochondrial crista remodeling and participates in maintaining mitochondrial structure and function. This study investigated whether the carnosic acid (CA) of rosemary protects the mitochondria of SH-SY5Y cells against the neurotoxicity of 6-hydroxydopamine (6-OHDA) by regulating Mic60. Our results showed that CA pretreatment reversed the reduction in the Mic60 and citrate synthase proteins, as well as the protein induction of PKA caused by 6-OHDA. Moreover, Mic60 and PINK1 siRNAs blocked the ability of CA to lessen the release of mitochondrial cytochrome c by 6-OHDA. As shown by immunoprecipitation assay, in 6-OHDA-treated cells, the interaction of Mic60 with its phosphorylated threonine residue was decreased, but the interaction with its phosphorylated serine residue was increased. PINK1 siRNA and forskolin, a PKA activator, reversed these interactions. Moreover, forskolin pretreatment prevented CA from rescuing the interaction of PINK1 and Mic60 and the reduction in cytochrome c release and mitophagy impairment in 6-OHDA-treated cells. In conclusion, CA prevents 6-OHDA-induced cytochrome c release by regulating Mic60 phosphorylation by PINK1 through a downregulation of PKA. The regulation of Mic60 by CA can be considered as a protective mechanism for the prevention of Parkinson's disease.
|Appears in Collections:||食品科學系|
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