%0 Journal Article
%T BL-918 activates PINK1/Parkin signaling pathway to ameliorate the progression of Parkinson's disease.
%A Wang Y
%A Luo S
%A Su H
%A Wang Z
%A Chu L
%A Zhang C
%J J Biol Chem
%V 300
%N 8
%D 2024 Jul 9
%M 38992440
暂无%R 10.1016/j.jbc.2024.107543
%X The pathogenesis of Parkinson's disease (PD) has been associated with mitochondrial dysfunction. Given that the PINK1/Parkin pathway governs mitochondrial quality control by inducing mitophagy to remove damaged mitochondria, therapeutic approaches to activate PINK1/Parkin-mediated mitophagy have the potential in the treatment of PD. Here, we have identified a new small molecule, BL-918, as an inducer of mitophagy via activating the PINK1/Parkin pathway. BL-918 triggers PINK1 accumulation and Parkin mitochondrial translocation to initiate PINK1/Parkin-mediated mitophagy. We found that mitochondrial membrane potential and mitochondrial permeability transition pore were involved in BL-918-induced PINK1/Parkin pathway activation. Moreover, we showed that BL-918 mitigated PD progression in MPTP-induced PD mice in a PINK1-dependent manner. Our results unravel a new activator of the PINK1/Parkin signaling pathway and provide a potential strategy for the treatment of PD and other diseases with dysfunctional mitochondria.