Institut für Biochemie und Molekularbiologie, ZBMZ, Universität Freiburg, 79104 Freiburg, Germany. Trinationales Graduiertenkolleg 1478, Universität Freiburg, 79104 Freiburg, Germany. Faculty of Biology, Universität Freiburg, 79104 Freiburg, Germany. BIOSS Centre for Biological Signalling Studies, Universität Freiburg, 79104 Freiburg, Germany.
Institut für Biochemie und Molekularbiologie, ZBMZ, Universität Freiburg, 79104 Freiburg, Germany.
Science. 2014 Nov 28;346(6213):1109-13. doi: 10.1126/science.1261253. Epub 2014 Nov 6.
Mitochondria play central roles in cellular energy conversion, metabolism, and apoptosis. Mitochondria import more than 1000 different proteins from the cytosol. It is unknown if the mitochondrial protein import machinery is connected to the cell division cycle. We found that the cyclin-dependent kinase Cdk1 stimulated assembly of the main mitochondrial entry gate, the translocase of the outer membrane (TOM), in mitosis. The molecular mechanism involved phosphorylation of the cytosolic precursor of Tom6 by cyclin Clb3-activated Cdk1, leading to enhanced import of Tom6 into mitochondria. Tom6 phosphorylation promoted assembly of the protein import channel Tom40 and import of fusion proteins, thus stimulating the respiratory activity of mitochondria in mitosis. Tom6 phosphorylation provides a direct means for regulating mitochondrial biogenesis and activity in a cell cycle-specific manner.
线粒体在细胞能量转换、代谢和细胞凋亡中起着核心作用。线粒体从细胞质中输入超过 1000 种不同的蛋白质。目前尚不清楚线粒体蛋白输入机制是否与细胞分裂周期有关。我们发现，细胞周期依赖性激酶 Cdk1 刺激了主要的线粒体入口门，即外膜转位酶（TOM），在有丝分裂中组装。这一分子机制涉及到由细胞周期蛋白 Clb3 激活的 Cdk1 对 Tom6 的细胞质前体的磷酸化，从而促进 Tom6 向线粒体的输入。Tom6 的磷酸化促进了蛋白输入通道 Tom40 的组装和融合蛋白的输入，从而刺激了线粒体在有丝分裂中的呼吸活性。Tom6 的磷酸化提供了一种直接的方式，以细胞周期特异性的方式调节线粒体的生物发生和活性。
