Department of Pathology, St. Jude Children's Research Hospital, Memphis, TN 38105-3678, USA.
Antioxid Redox Signal. 2011 May 15;14(10):1953-8. doi: 10.1089/ars.2010.3809. Epub 2011 Mar 18.
A fundamental function of autophagy conserved from yeast to mammals is mobilization of macromolecules during times of limited nutrient availability, permitting organisms to survive under starvation conditions. In yeast, autophagy is initiated following nitrogen or carbon deprivation, and autophagy mutants die rapidly under these conditions. Similarly, in mammals, autophagy is upregulated in most organs following initiation of starvation, and is critical for survival in the perinatal period following abrupt termination of the placental nutrient supply. The nutrient-sensing kinase, mammalian target of rapamycin, coordinates cellular proliferation and growth with nutrient availability, at least in part by regulating protein synthesis and autophagy-mediated degradation. This review focusses on the regulation of autophagy by Tor, a mammalian target of rapamycin, and Ulk1, a mammalian homolog of Atg1, in response to changes in nutrient availability. Given the importance of mitochondria in maintaining bioenergetic homestasis, and potentially as a source of membrane for autophagosomes during starvation, possible roles for mitochondria in this process are also discussed.
自噬的一个基本功能是在营养有限的情况下动员大分子，使生物能够在饥饿条件下存活。在酵母中，自噬是在氮或碳饥饿后开始的，自噬突变体在这些条件下迅速死亡。同样，在哺乳动物中，饥饿启动后，大多数器官中的自噬都会上调，并且在胎盘营养供应突然终止后，在围产期对于生存至关重要。营养感应激酶，雷帕霉素靶蛋白，至少部分通过调节蛋白质合成和自噬介导的降解，将细胞增殖和生长与营养可用性协调起来。这篇综述集中讨论了雷帕霉素靶蛋白的哺乳动物靶点 Tor 和 Atg1 的哺乳动物同源物 Ulk1 对营养可用性变化的自噬调节。鉴于线粒体在维持生物能量稳态中的重要性，以及在饥饿期间可能作为自噬体的膜源，因此也讨论了线粒体在这一过程中的可能作用。
