[ Back to EurekAlert! ] Public release date: 19-Apr-2010
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Contact: Rita Sullivan
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Rockefeller University Press

New insight into Parkinson's disease

New research provides crucial insight into the pathogenic mechanisms of Parkinson's disease (PD), a prevalent neurodegenerative disorder. The study appears in the April 19 issue of the Journal of Cell Biology (www.jcb.org).

The identification of inherited mutations in genes such as Parkin and PINK1 ( PTEN-induced putative kinase 1 ) has revealed key factors in the development of familial forms of the disease. Parkin adds ubiquitin molecules to other proteins to trigger their degradation, while PINK1 regulates mitochondrial quality control. But how these two genes work together remains a mystery.

Now, Keiji Tanaka and colleagues show that PINK1 is rapidly and continuously degraded under steady-state conditions when mitochondria are healthy, and that a loss in mitochondrial membrane potential stabilizes PINK1's accumulation. Furthermore, PINK1 recruits Parkin from the cytoplasm to mitochondria with low membrane potential to initiate the disposal of damaged mitochondria. Interestingly, the ubiquitin ligase activity of Parkin is repressed in the cytoplasm under steady-state conditions; however, PINK1-dependent mitochondrial localization liberates the latent enzymatic activity of Parkin. Some pathogenic mutations of PINK1 and Parkin interfere with the aforementioned events, suggesting they play a role in causing the disease.

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About The Journal of Cell Biology

Founded in 1955, The Journal of Cell Biology (JCB) is published by The Rockefeller University Press. All editorial decisions on manuscripts submitted are made by active scientists in conjunction with our in-house scientific editors. JCB content is posted to PubMed Central, where it is available to the public for free six months after publication. Authors retain copyright of their published works and third parties may reuse the content for non-commercial purposes under a creative commons license. For more information, please visit www.jcb.org.

Matsuda, N., et al. 2010. J. Cell Biol. doi:10.1083/jcb.200910140.



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