Tricornered/NDR kinase signaling mediates PINK1-directed mitochondrial quality control and tissue maintenance.
Tricornered/NDR kinase signaling mediates PINK1-directed mitochondrial quality control and tissue maintenance.
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DOI：
10.1101/gad.203406.112
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发表时间：
2013-01
影响因子：
10.5
通讯作者：
Zhihao Wu-;Tomoyo Sawada;K. Shiba;Song Liu;T. Kanao;R. Takahashi;N. Hattori;Y. Imai;B. Lu
中科院分区：
文献类型：
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作者：
Zhihao Wu-;Tomoyo Sawada;K. Shiba;Song Liu;T. Kanao;R. Takahashi;N. Hattori;Y. Imai;B. Lu
真核生物采用精细的线粒体质量控制（MQC）来维持产生能量的细胞器的功能。帕金森病相关的PINK1和Parkin积极参与MQC。然而，所涉及的信号事件在很大程度上是未知的。在这里，我们发现雷帕霉素2 （mTORC2）和三角角激酶（Trc）的机制靶标在PINK1的下游作用，调节MQC。Trc以依赖mTORC2和不依赖mTORC2的方式磷酸化，并在响应PINK1时特异性定位于线粒体，PINK1通过线粒体复合物- 1活性调节mTORC2。遗传上，mTORC2和Trc作用于Parkin的上游。因此，多重激酶信号在PINK1和Parkin之间起作用，调节MQC，这一过程在哺乳动物中高度保守。
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.