Noda T, Ohsumi Y
National Institute for Basic Biology, Department of Cell Biology, Nishigonaka 38, Myodaijicho, Okazaki 444, Japan.
J Biol Chem. 1998 Feb 13;273(7):3963-6. doi: 10.1074/jbc.273.7.3963.
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, Saccharomyces 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.
自噬是一种由饥饿诱导的大量蛋白质降解过程。自噬诱导的控制机制尚未完全了解。我们发现，Tor，一种磷脂酰肌醇激酶同源物，参与了酿酒酵母中自噬的控制。当添加雷帕霉素（一种Tor功能抑制剂）时，即使在富含营养的培养基中生长的细胞中也会诱导自噬。一个温度敏感的tor突变体在非允许温度下也会导致自噬的诱导。这些结果表明Tor对自噬的诱导起负调节作用。Tor是第一个被确定为自噬饥饿信号通路中关键参与者的分子。此外，我们发现高浓度的cAMP对自噬的诱导有抑制作用。APG基因产物参与饥饿诱导的自噬。在雷帕霉素存在的情况下，apg突变体中不会诱导自噬，这表明Tor的作用位点在Apg蛋白的作用位点上游。在富含营养的培养基中，Apg蛋白也参与氨肽酶I从细胞质到液泡的转运。Tor可能起到在自噬和氨肽酶I转运之间切换Apg功能的作用。
