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Mutations in the PINK1 and PARK2 genes are associated with Parkinson's disease, and the corresponding proteins Pink1 and Parkin are critical in the removal of damaged mitochondria.Atypical Rho GTPase Miro1 is an outer mitochondrial membrane protein involved in mitochondrial trafficking.It has been shown that Miro1 is a substrate of the PINK1/Parkin mitochondrial quality control system, as it is ubiquitinated by Parkin and subsequently degraded by the proteasome upon mitochondrial depolarization induced by uncouplers.We have previously reported activation of mitochondrial destruction and loss in primary cortical neurons that overexpress mutant A53T α-synuclein, one of the major components of Lewy bodies in Parkinson's disease.We have performed mass-spectrometry analysis of the Miro1 interactome in HEK cells with and without treatment with an uncoupler.We have found that α-synuclein interacts with Miro1 and that this interaction was lost after treatment with the uncoupler.Because Miro1 is one of the key proteins involved in mitochondrial dynamics (mitochondrial motility, fusion-fission dynamics and mitophagy), we studied further whether wt or A53T mutant α-synuclein affect mitochondrial dynamics and Miro functions.Overexpression of α-synucleins affected neither mitochondrial motility nor fusion rate.However, overexpression of A53T α-synuclein lead to increased mitophagy as estimated by co-localization of mitochondria with the autophagosome marker RFP-LC3-EGFP.Moreover, mitophagy induced by overexpressing A53T mutant α-synuclein was strongly supressed when Miro1 was co-expressed.Notably,overexpression of Miro itself does not affect mitophagy.We also performed a co-immunoprecititation of endogenous Miro1 in an c-synuclein over-expressing dopaminergic SHSY5Y cell line.However, we failed to show a direct interaction of Miro1 with α-synuclein.Together, these results suggest that Miro and α-synuclein may interact in the mitophagic pathway.