Tricornered/NDR kinase signaling mediates PINK1-directed mitochondrial quality control and tissue maintenance.
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.
Department of Pathology, Stanford University School of Medicine, Stanford, California 94305, USA.
Zhihao
Z
Wu
Tomoyo
T
Sawada
Kahori
K
Shiba
Song
S
Liu
Tomoko
T
Kanao
Ryosuke
R
Takahashi
Nobutaka
N
Hattori
Yuzuru
Y
Imai
Bingwei
B
Lu
D000818:Animals; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008297:Male; D008928:Mitochondria / Q000378:metabolism*; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D000099202:PTEN-Induced Putative Kinase
D029721:Drosophila Proteins; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; C419769:trc protein, Drosophila; C534484:PINK1 protein, Drosophila; D000099202:PTEN-Induced Putative Kinase