Parkin promotes the ubiquitination and degradation of the mitochondrial fusion factor mitofusin 1
Article first published online: 6 JUN 2011
© 2011 The Authors. Journal of Neurochemistry © 2011 International Society for Neurochemistry
Journal of Neurochemistry
Volume 118, Issue 4, pages 636–645, August 2011
How to Cite
Glauser, L., Sonnay, S., Stafa, K. and Moore, D. J. (2011), Parkin promotes the ubiquitination and degradation of the mitochondrial fusion factor mitofusin 1. Journal of Neurochemistry, 118: 636–645. doi: 10.1111/j.1471-4159.2011.07318.x
- Issue published online: 14 JUL 2011
- Article first published online: 6 JUN 2011
- Accepted manuscript online: 25 MAY 2011 11:37AM EST
- Received January 27, 2011; revised manuscript received May 3, 2011; accepted May 10, 2011.
- Parkinson’s disease;
J. Neurochem. (2011) 118, 636–645.
Mutations in the parkin gene cause early-onset, autosomal recessive Parkinson’s disease. Parkin functions as an E3 ubiquitin ligase to mediate the covalent attachment of ubiquitin monomers or linked chains to protein substrates. Substrate ubiquitination can target proteins for proteasomal degradation or can mediate a number of non-degradative functions. Parkin has been shown to preserve mitochondrial integrity in a number of experimental systems through the regulation of mitochondrial fission. Upon mitochondrial damage, parkin translocates to mitochondria to mediate their selective elimination by autophagic degradation. The mechanism underlying this process remains unclear. Here, we demonstrate that parkin interacts with and selectively mediates the atypical poly-ubiquitination of the mitochondrial fusion factor, mitofusin 1, leading to its enhanced turnover by proteasomal degradation. Our data supports a model whereby the translocation of parkin to damaged mitochondria induces the degradation of mitofusins leading to impaired mitochondrial fusion. This process may serve to selectively isolate damaged mitochondria for their removal by autophagy.