PINK1-Mediated Phosphorylation of Parkin Boosts Parkin Activity in

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Parkinson's disease is a neurodegenerative disorder caused by degeneration of the midbrain dopaminergic system in addition to other nervous systems. PINK1 and parkin, which encode protein kinase and ubiquitin-ligase, respectively, were identified as the genes responsible for the autosomal recessive form of juvenile Parkinson's disease. These two enzymes are involved in mitochondrial maintenance. Although we previously found that Parkin is phosphorylated by PINK1 in mammalian cultured cells, the physiological significance of this interaction in vivo remained unclear. Here, we describe that the phosphorylation of Parkin altered mitochondrial morphology and function in muscle tissue through the degradation of mitochondrial GTPase proteins (such as Mitofusin and Miro) and a mitochondrial respiratory complex I subunit by increasing its ubiquitin-ligase activity. We also found that the dopaminergic expression of both constitutively phosphorylated and non-phosphorylated forms of Parkin affects the flight activity and shortens the lifespan of flies, suggesting that the appropriate phosphorylation of Parkin is important for both dopaminergic activity and the survival of dopaminergic neurons.

Vyšlo v časopise: PINK1-Mediated Phosphorylation of Parkin Boosts Parkin Activity in. PLoS Genet 10(6): e32767. doi:10.1371/journal.pgen.1004391
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004391

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