Principe Felipe Research Centre, C/Eduardo Primo Yúfera 3, Valencia 46012, Spain.
Cells. 2012 Jul 27;1(3):372-95. doi: 10.3390/cells1030372.
Autophagy is an evolutionarily conserved process that contributes to maintain cell homeostasis. Although it is strongly regulated by many extracellular factors, induction of autophagy is mainly produced by starvation of nutrients. In mammalian cells, the regulation of autophagy by amino acids, and also by the hormone insulin, has been extensively investigated, but knowledge about the effects of other autophagy regulators, including another nutrient, glucose, is more limited. Here we will focus on the signalling pathways by which environmental glucose directly, i.e., independently of insulin and glucagon, regulates autophagy in mammalian cells, but we will also briefly mention some data in yeast. Although glucose deprivation mainly induces autophagy via AMPK activation and the subsequent inhibition of mTORC1, we will also comment other signalling pathways, as well as evidences indicating that, under certain conditions, autophagy can be activated by glucose. A better understanding on how glucose regulates autophagy not only will expand our basic knowledge of this important cell process, but it will be also relevant to understand common human disorders, such as cancer and diabetes, in which glucose levels play an important role.
自噬是一种进化上保守的过程,有助于维持细胞内环境稳定。尽管它受到许多细胞外因素的强烈调控,但自噬的诱导主要是由营养物质的饥饿引起的。在哺乳动物细胞中,氨基酸对自噬的调节,以及激素胰岛素对自噬的调节,已经得到了广泛的研究,但对其他自噬调节剂(包括另一种营养物质葡萄糖)的作用的了解则更为有限。在这里,我们将重点介绍环境葡萄糖直接(即独立于胰岛素和胰高血糖素)调节哺乳动物细胞自噬的信号通路,但我们也将简要提及一些酵母中的相关数据。虽然葡萄糖剥夺主要通过 AMPK 激活和随后的 mTORC1 抑制来诱导自噬,但我们也将讨论其他信号通路,以及表明在某些条件下葡萄糖可以激活自噬的证据。更好地了解葡萄糖如何调节自噬,不仅将扩展我们对这一重要细胞过程的基础知识,而且对于理解癌症和糖尿病等常见人类疾病也具有重要意义,这些疾病中葡萄糖水平起着重要作用。