代谢调控细胞死亡的研究进展

Research progress on metabolic regulating cell fate

代谢和细胞死亡之间的密切联系逐渐受到越来越多的关注.许多与代谢相关的蛋白在细胞程序性死亡通路中起着关键性作用.一些曾被认为参与调节细胞死亡的蛋白也被证实有调控代谢环路的作用.此外,很多代谢中间产物都密切参与影响细胞死亡的信号转导通路的级联反应.某些代谢调控点不仅接收代谢变量传来的信息,而且能够发送调控细胞生存的信号.通常,这些调控点通过激活某一细胞器或在细胞整体水平上启动适应性反应来应对代谢失调,从而建立新的稳态.然而,当代谢紊乱过于严重或持续时间过长时,这些代谢调控点将启动凋亡或程序性坏死等方式调控细胞死亡.对细胞代谢和死亡通路的交叉调控进行探讨,以期为基于靶向代谢途径阻断或诱导细胞死亡的新药研发提供线索.

The close link between metabolism and cell death has been getting more and more attention.Many metabolically related proteins play a key role in the programmed cell death pathway.Several proteins classically regulating cell death have been found to regulate metabolism.In addition,many metabolic intermediates are closely involved in the cascade of signal transduction pathways that influence cell death.Some metabolic checkpoints not only receive information from metabolic variables,but also transmit signals that regulate cell survival.Typically,these checkpoints respond to metabolic imbalances by activating an organelle specific or by initiating an adaptive response at the overall level of the cell,and attempts to establish a new homeostasis.However,when the metabolic disorders are extravagantly serious or prolonged in time,these checkpoints will initiate apoptosis or programmed cell death.The cross-regulation of cellular metabolism and death pathways was discussed,so as to provide clues for the development of novel pharmacological approaches by regulating the metabolism to block or induced cell death.