The mitochondrial fusion-promoting factor mitofusin is a substrate of the PINK1/parkin pathway.
The mitochondrial fusion-promoting factor mitofusin is a substrate of the PINK1/parkin pathway.
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DOI：
10.1371/journal.pone.0010054
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发表时间：
2010-04-07
期刊：
影响因子：
3.7
通讯作者：
Pallanck L
中科院分区：
文献类型：
--
作者：
Poole AC;Thomas RE;Yu S;Vincow ES;Pallanck L
Loss-of-function mutations in the PINK1 or parkin genes result in recessive heritable forms of parkinsonism. Genetic studies of Drosophila orthologs of PINK1 and parkin indicate that PINK1, a mitochondrially targeted serine/threonine kinase, acts upstream of Parkin, a cytosolic ubiquitin-protein ligase, to promote mitochondrial fragmentation, although the molecular mechanisms by which the PINK1/Parkin pathway promotes mitochondrial fragmentation are unknown. We tested the hypothesis that PINK1 and Parkin promote mitochondrial fragmentation by targeting core components of the mitochondrial morphogenesis machinery for ubiquitination. We report that the steady-state abundance of the mitochondrial fusion-promoting factor Mitofusin (dMfn) is inversely correlated with the activity of PINK1 and Parkin in Drosophila. We further report that dMfn is ubiquitinated in a PINK1- and Parkin-dependent fashion and that dMfn co-immunoprecipitates with Parkin. By contrast, perturbations of PINK1 or Parkin did not influence the steady-state abundance of the mitochondrial fission-promoting factor Drp1 or the mitochondrial fusion-promoting factor Opa1, or the subcellular distribution of Drp1. Our findings suggest that dMfn is a direct substrate of the PINK1/Parkin pathway and that the mitochondrial morphological alterations and tissue degeneration phenotypes that derive from mutations in PINK1 and parkin result at least in part from reduced ubiquitin-mediated turnover of dMfn.
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DOI：
10.1016/j.bbrc.2008.11.086
发表时间：
2009-01-16
影响因子：
3.1
作者：
Park, Jeehye;Lee, Gina;Chung, Jongkyeong
通讯作者：
Chung, Jongkyeong
DOI：
10.1083/jcb.200809125
发表时间：
2008-12-01
期刊：
The Journal of cell biology
影响因子：
--
作者：
Narendra D;Tanaka A;Suen DF;Youle RJ
通讯作者：
Youle RJ
影响因子：
2.6
作者：
Hwa, JJ;Hiller, MA;Santel, A
通讯作者：
Santel, A
影响因子：
64.8
作者：
Clark, Ira E.;Dodson, Mark W.;Guo, Ming
通讯作者：
Guo, Ming
影响因子：
64.8
作者：
Park, Jeehye;Lee, Sung Bae;Chung, Jongkyeong
通讯作者：
Chung, Jongkyeong