Mitochondrial Regulation by PINK1-Parkin Signaling.

Two genes responsible for the juvenile Parkinson's disease (PD), PINK1 and Parkin, have been implicated in mitochondrial quality control. The inactivation of PINK1, which encodes a mitochondrial kinase, leads to age-dependent mitochondrial degeneration in Drosophila. The phenotype is closely associated with the impairment of mitochondrial respiratory chain activity and defects in mitochondrial dynamics. Drosophila genetic studies have further revealed that PINK1 is an upstream regulator of Parkin and is involved in the mitochondrial dynamics and motility. A series of cell biological studies have given rise to a model in which the activation of PINK1 in damaged mitochondria induces the selective elimination of mitochondria in cooperation with Parkin through the ubiquitin-proteasome and autophagy machineries. Although the relevance of this pathway to PD etiology is still unclear, approaches using stem cells from patients and animal models will help to understand the significance of mitochondrial quality control by the PINK1-Parkin pathway in PD and in healthy individuals. Here I will review recent advances in our understanding of the PINK1-Parkin signaling and will discuss the roles of PINK1-Parkin signaling for mitochondrial maintenance and how the failure of this signaling leads to neurodegeneration. [ABSTRACT FROM AUTHOR]

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