Back to Search
Start Over
Proteasome and p97 mediate mitophagy and degradation of mitofusins induced by Parkin
- Source :
- The Journal of Cell Biology. Dec 27, 2010, Vol. 191 Issue 7, p1367, 14 p.
- Publication Year :
- 2010
-
Abstract
- Damage to mitochondria can lead to the depolarization of the inner mitochondrial membrane, thereby sensitizing impaired mitochondria for selective elimination by autophagy. However, fusion of uncoupled mitochondria with polarized mitochondria can compensate for damage, reverse membrane depolarization, and obviate mitophagy. Parkin, an E3 ubiquitin ligase that is mutated in monogenic forms of Parkinson's disease, was recently found to induce selective autophagy of damaged mitochondria. Here we show that ubiquitination of mitofusins Mfn1 and Mfn2, large GTPases that mediate mitochondrial fusion, is induced by Parkin upon membrane depolarization and leads to their degradation in a proteasome- and p97-dependent manner, p97, a AAA+ ATPase, accumulates on mitochondria upon uncoupling of Parkin-expressing cells, and both p97 and proteasome activity are required for Parkin-mediated mitophagy. After mitochondrial fission upon depolarization, Parkin prevents or delays refusion of mitochondria, likely by the elimination of mitofusins. Inhibition of Drp1mediated mitochondrial fission, the proteasome, or p97 prevents Parkin-induced mitophagy. doi/ 10.1083/jcb.201007013
- Subjects :
- Adenosine triphosphatase -- Research
Adenosine triphosphatase -- Properties
Mitochondria -- Research
Ubiquitin-proteasome system -- Research
Proteins -- Research
Proteins -- Properties
Ligases -- Properties
Ligases -- Research
Guanosine triphosphatase -- Research
Guanosine triphosphatase -- Properties
Biological sciences
Subjects
Details
- Language :
- English
- ISSN :
- 00219525
- Volume :
- 191
- Issue :
- 7
- Database :
- Gale General OneFile
- Journal :
- The Journal of Cell Biology
- Publication Type :
- Academic Journal
- Accession number :
- edsgcl.246011978