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Published online November 24, 2008
doi:10.1083/jcb.200809125
The Journal of Cell Biology, Vol. 183, No. 5, 795-803
The Rockefeller University Press, 0021-9525 $30.00
© 2008 Narendra et al.
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Parkin is recruited selectively to impaired mitochondria and promotes their autophagy



Derek Narendra1,2, Atsushi Tanaka1, Der-Fen Suen1, and Richard J. Youle1

1 Biochemistry Section, Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892
2 Howard Hughes Medical Institute National Institutes of Health Research Scholars Program, Bethesda, MD 20814

Correspondence to Richard J. Youle: youler{at}ninds.nih.gov

Loss-of-function mutations in Park2, the gene coding for the ubiquitin ligase Parkin, are a significant cause of early onset Parkinson's disease. Although the role of Parkin in neuron maintenance is unknown, recent work has linked Parkin to the regulation of mitochondria. Its loss is associated with swollen mitochondria and muscle degeneration in Drosophila melanogaster, as well as mitochondrial dysfunction and increased susceptibility to mitochondrial toxins in other species. Here, we show that Parkin is selectively recruited to dysfunctional mitochondria with low membrane potential in mammalian cells. After recruitment, Parkin mediates the engulfment of mitochondria by autophagosomes and the selective elimination of impaired mitochondria. These results show that Parkin promotes autophagy of damaged mitochondria and implicate a failure to eliminate dysfunctional mitochondria in the pathogenesis of Parkinson's disease.

Abbreviations used in this paper: au, arbitrary units; CCCP, carbonyl cyanide m-chlorophenylhydrazone; Drp1, dynamin-related protein 1; FLIP, fluorescence loss in photobleaching; Mfn, mitofusin; MEF, mouse embryonic fibroblast; ROI, region of interest; vMIA, viral mitochondrial-associated inhibitor of apoptosis; WT, wild type.

© 2008 Narendra et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jcb.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).


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Parkin cleans house
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