Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Tianjin Medical University, 22 Qixiangtai Road, Heping District, Tianjin, 300070, China.
Adv Exp Med Biol. 2019;1206:667-696. doi: 10.1007/978-981-15-0602-4_29.
Autophagy, which is one of the most important ways to maintain cell homeostasis plays an important regulatory role in cell survival and death. Currently, it is agreed that autophagy promotes or inhibits cell death depending on the internal and external environment and cell type. On the one hand, under normal nutritional conditions autophagy regulates cell survival by energy sensing through the main energy sensing cascade kinases. On the other hand, autophagy regulates the process of cell death. mTOR, Beclin 1, caspases, FLIPs, DAPK, and Tp53 play important regulatory roles in autophagy and apoptosis highlighting the crosstalk between the mechanisms underlying the two death modes. However, energy deficiency caused by PARP1 over-activation and DAPK-PKD pathway activation induces necrosis and autophagy, highlighting the interaction between the two pathways. In addition, autophagy regulates cell death through epigenetic regulation such as histone modification. More investigations on the relationship between autophagy and cell death is ongoing. In the future, there will be more challenges in the study of the relationship between autophagy and cell survival and death. As research increasingly focuses on cell death, the relationship between autophagy and existing and newly discovered cell death types is likely to become more complex. The elucidation of the regulatory role of autophagy in cell survival and death requires more research. Some research results are likely to provide hot topics for further investigations on diseases related to cell death disorders and an experimental basis for the targeted regulation of autophagy for specific treatment of diseases.
自噬是维持细胞内环境稳定的最重要途径之一，在细胞存活和死亡中起着重要的调节作用。目前，人们普遍认为自噬通过主要能量感应级联激酶在内外环境和细胞类型的影响下促进或抑制细胞死亡。一方面，在正常营养条件下，自噬通过能量感应来调节细胞存活。另一方面，自噬调节细胞死亡的过程。mTOR、Beclin 1、caspases、FLIPs、DAPK 和 Tp53 在自噬和细胞凋亡中发挥着重要的调节作用，突出了两种死亡模式的机制之间的串扰。然而，由于 PARP1 过度激活和 DAPK-PKD 途径的激活导致能量缺乏，从而诱导坏死和自噬，突出了这两条途径之间的相互作用。此外，自噬通过组蛋白修饰等表观遗传调控来调节细胞死亡。自噬与细胞死亡之间的关系的研究正在进行中。在未来，自噬与细胞存活和死亡之间关系的研究将面临更多的挑战。随着研究越来越关注细胞死亡，自噬与现有的和新发现的细胞死亡类型之间的关系可能变得更加复杂。阐明自噬在细胞存活和死亡中的调节作用需要更多的研究。一些研究结果可能为与细胞死亡紊乱相关的疾病的进一步研究提供热点，为针对自噬的特定治疗疾病的靶向调节提供实验基础。
