Tor, a phosphatidylinositol kinase homologue, controls autophagy in yeast
Tor, a phosphatidylinositol kinase homologue, controls autophagy in yeast
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DOI：
10.1074/jbc.273.7.3963
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发表时间：
1998-02-13
影响因子：
4.8
通讯作者：
Ohsumi, Y
中科院分区：
文献类型：
--
作者：
Noda, T;Ohsumi, Y
自噬是由饥饿诱导的大量蛋白质降解过程，诱导自噬的控制机制尚不清楚，我们发现Tor，一种磷脂酰肌醇激酶同源物，参与了酿酒酵母Sac Charomyces cerevisiae中自噬的控制，当加入Tor功能抑制剂雷帕霉素时，即使在营养丰富的培养基中生长的细胞也能诱导自噬，一个温度敏感的tor突变体也会导致在非允许温度下诱导自噬。这些结果表明，Tor负调控自噬的诱导，Tor是第一个被鉴定为自噬饥饿信号通路中的关键参与者的分子。此外，我们发现高浓度的cAMP抑制自噬的诱导，APG基因产物参与饥饿诱导的自噬，在雷帕霉素存在下apg突变体中不诱导自噬，在营养丰富的培养基中，Apg蛋白还参与了氨肽酶I从胞质到液泡的转运，Tor可能在自噬和转运氨肽酶I之间起着转换Apg功能的作用。
Autophagy is a bulk protein degradation process that is induced by starvation, The control mechanism for induction of autophagy is not well understood, We found that Tor, a phosphatidylinositol kinase homologue, is involved in the control of autophagy in the yeast, Sac charomyces cerevisiae, When rapamycin, an inhibitor of Tor function, is added, autophagy is induced even in cells growing in nutrient-rich medium, A temperature-sensitive tor mutant also leads to induction of autophagy at a nonpermissive temperature. These results indicate that Tor negatively regulates the induction of autophagy, Tor is the first molecule that is identified as a pivotal player in the starvation-signaling pathway of autophagy, Furthermore, we found that a high concentration of cAMP is inhibitory for induction of autophagy, APG gene products are involved in autophagy induced by starvation, Autophagy was not induced in apg mutants in the presence of rapamycin, indicating that the site of action of Tor is upstream of those of Apg proteins, In nutrient-rich medium, Apg proteins are involved also in the transport of aminopeptidase I from the cytosol to the vacuole, Tor may act to switch Apg function between autophagy and transport of aminopeptidase I.