New insight into Parkinson's disease

Apr 19, 2010

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.

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 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 .

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.

Explore further: How do our muscles work? Scientists reveal important new insights into muscle protein

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

add to favorites email to friend print save as pdf

Related Stories

When cells run out of fuel

Aug 24, 2009

Parkinson's disease is caused by the degeneration of neurons in the midbrain. The mechanisms leading to the loss of these neurons, however, are largely unknown. Recent research revealed that about ten per cent of cases are ...

Recommended for you

How calcium regulates mitochondrial carrier proteins

17 hours ago

Mitochondrial carriers are a family of proteins that play the key role of transporting a chemically diverse range of molecules across the inner mitochondrial membrane. Mitochondrial aspartate/glutamate carriers are part of ...

Team conducts unprecedented analysis of microbial ecosystem

18 hours ago

An international team of scientists from the Translational Genomics Research Institute (TGen) and The Luxembourg Centre for Systems Biomedicine (LCSB) have completed a first-of-its-kind microbial analysis of a biological ...

Students create microbe to weaken superbug

Nov 25, 2014

A team of undergraduate students from the University of Waterloo have designed a synthetic organism that may one day help doctors treat MRSA, an antibiotic-resistant superbug.

User comments : 0

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.