Journal
GENES & DEVELOPMENT
Volume 27, Issue 2, Pages 157-162Publisher
COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
DOI: 10.1101/gad.203406.112
Keywords
Tricornered; NDR; mTORC2; PINK1; mitochondrial quality control
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Funding
- NIH [R01AR054926, R01MH080378]
- MEXT in Japan
- CREST program of JST
- Ministry of Health, Labor, and Welfare in Japan
- Grants-in-Aid for Scientific Research [23790973] Funding Source: KAKEN
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Eukaryotes employ elaborate mitochondrial quality control (MQC) to maintain the function of the power-generating organelle. Parkinson's disease-associated PINK1 and Parkin actively participate in MQC. However, the signaling events involved are largely unknown. Here we show that mechanistic target of rapamycin 2 (mTORC2) and Tricornered (Trc) kinases act downstream from PINK1 to regulate MQC. Trc is phosphorylated in mTORC2-dependent and mTORC2-independent manners and is specifically localized to mitochondria in response to PINK1, which regulates mTORC2 through mitochondrial complex-I activity. Genetically, mTORC2 and Trc act upstream of Parkin. Thus, multiplex kinase signaling is acting between PINK1 and Parkin to regulate MQC, a process highly conserved in mammals.
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