Validation Of The Potential PINK1 Substrate

The Parkinson's disease(PD)-related PINK1(PTEN induced putative kinase 1)is indispensable to maintain the homeostasis of dopaminergic neurons.Upon mitochondrial depolarization,PINK1 phosphorylates its substrates to trigger autophagy or selective autophagy.Excepting mitophagy-dependent functions of PINK1,other mitophagy-independent or joint mechanism functions of PINK1 and their possible roles in The Parkinson's disease worth exploring.Based on the proteomics and phosphoproteomics result of carbonyl cyanide m-chlorophenylhydrazone(CCCP)treated primary neuron from wild type and PINK1 knockout mice,phosphorylation levels of all potential targets of PINK1 were carefully analyzed.We found that the phosphorylation levels of site Ser289,site Ser333 of DAPK1 and site Ser757,site Ser555 of ULK1 may change depended on PINK1 kinase activity.We also fund that the phosphorylation levels of ERK and AMPK were up with the treatment of CCCP independent of PINK1.This research explored the potential downstream substrates of PINK1 and supported the references for refining the signaling pathways of PINK1 in the Parkinson Disease.