Alibhoy Abbas A, Chiang Hui-Ling
Department of Cellular and Molecular Physiology; Penn State College of Medicine; Hershey, PA USA.
Commun Integr Biol. 2010 Nov;3(6):594-6. doi: 10.4161/cib.3.6.13241. Epub 2010 Nov 1.
Upon starving Saccharomyces cerevisiae of glucose, the key gluconeogenic enzymes fructose-1,6-bisphosphatase (FBPase), malate dehydrogenase (MDH2), isocitrate lyase (Icl1p) and phosphoenolpyruvate carboxykinase (Pck1p) are induced. When glucose is added to cells that have been starved for 3 days, these gluconeogenic enzymes are degraded in the vacuole via the vacuole import and degradation (Vid) pathway. Moreover, it has been determined that during glucose starvation, these cargo proteins interact with the target of rapamycin complex 1 (TORC1), which is comprised of Tor1p, Tco89p, Lst8p and Kog1p. However, following glucose replenishment, Tor1p dissociates from the cargo proteins. We have determined that cells overexpressing TOR1 inhibited the phosphorylation of FBPase and its subsequent degradation in the vacuole. Interestingly, while the deletion of TCO89 inhibited FBPase degradation, it did not inhibit the phosphorylation of FBPase. Both Tor1p and Tco89p were found in endosomes originating from the plasma membrane as well as in retrograde vesicles forming from the vacuole membrane. Here we further discuss our findings and elaborate on our current model of the Vid pathway.
在使酿酒酵母缺乏葡萄糖时，关键的糖异生酶1,6 - 二磷酸果糖酶（FBPase）、苹果酸脱氢酶（MDH2）、异柠檬酸裂解酶（Icl1p）和磷酸烯醇式丙酮酸羧激酶（Pck1p）会被诱导产生。当向饥饿3天的细胞中添加葡萄糖时，这些糖异生酶会通过液泡导入和降解（Vid）途径在液泡中被降解。此外，已经确定在葡萄糖饥饿期间，这些货物蛋白与雷帕霉素靶蛋白复合物1（TORC1）相互作用，TORC1由Tor1p、Tco89p、Lst8p和Kog1p组成。然而，在补充葡萄糖后，Tor1p会从货物蛋白上解离。我们已经确定过表达TOR1的细胞会抑制FBPase的磷酸化及其随后在液泡中的降解。有趣的是，虽然TCO89的缺失会抑制FBPase的降解，但它不会抑制FBPase的磷酸化。Tor1p和Tco89p都存在于源自质膜的内体以及由液泡膜形成的逆行小泡中。在此我们进一步讨论我们的发现，并详细阐述我们目前的Vid途径模型。
