Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.


Sci. Signal., 16 December 2008
Vol. 1, Issue 50, p. ec433
[DOI: 10.1126/scisignal.150ec433]


Autophagy Damage Control for Mitochondria

Wei Wong

Science Signaling, AAAS, Washington, DC 20005, USA

The most commonly mutated gene in familial Parkinson’s disease is PARK2, which encodes the ubiquitin E3 ligase Parkin. Narendra et al. noticed that endogenous Parkin, which normally displays a cytosolic distribution, was localized to smaller, fragmented mitochondria in a subset of human embryonic kidney (HEK) 293 cells. Parkin accumulation on mitochondria was increased when cells were exposed to carbonyl cyanide m-chlorophenylhydrazone (CCCP), which uncouples the electron transport chain and causes mitochondrial depolarization. Parkin tagged with yellow fluorescent protein (YFP-Parkin) also translocated to mitochondria after CCCP treatment in HeLa cells (which have low amounts of endogenous Parkin). Parkin accumulation was not caused by morphological changes in mitochondria, such as fragmentation or fission, but instead correlated with membrane depolarization, suggesting that Parkin selectively localized to damaged mitochondria. Volumetric measurements revealed that, in YFP-Parkin–containing HeLa cells but not cells without exogenous Parkin, mitochondria decreased in mass, then disappeared after CCCP treatment, an observation confirmed by the inability of cells without mitochondria to survive in media containing galactose instead of glucose. Parkin colocalized with microtubule-associated protein light chain 3 (LC3), an autophagosome marker, which suggests that Parkin recruitment to mitochondria initiated autophagic degradation of the damaged organelles. Indeed, autophagy of mitochondria was blocked by inhibitors of lysosomal function or autophagosome formation, supporting this conclusion. More important, mouse embryonic fibroblasts lacking a key component of the autophagy pathway, autophagy-related 5 homolog (ATG5), retained their mitochondria after CCCP treatment, even though YFP-Parkin translocated to the mitochondria in these cells. In the associated commentary, McBride suggests that loss of Parkin recruitment to dysfunctional mitochondria may precede the neurodegeneration seen in Parkinson’s disease.

D. Narendra, A. Tanaka, D.-F. Suen, R. J. Youle, Parkin is recruited selectively to impaired mitochondria and promotes their autophagy. J. Cell Biol. 183, 795–803 (2008). [Abstract] [Full Text]

H. M. McBride, Parkin mitochondria in the autophagosome. J. Cell Biol. 183, 757–759 (2008). [Abstract] [Full Text]

Citation: W. Wong, Damage Control for Mitochondria. Sci. Signal. 1, ec433 (2008).

To Advertise     Find Products

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882