Department of Pharmacology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, U.S.A.
Essays Biochem. 2013;55:105-17. doi: 10.1042/bse0550105.
Autophagy is intimately associated with eukaryotic cell death and apoptosis. Indeed, in some cases the same proteins control both autophagy and apoptosis. Apoptotic signalling can regulate autophagy and conversely autophagy can regulate apoptosis (and most likely other cell death mechanisms). However, the molecular connections between autophagy and cell death are complicated and, in different contexts, autophagy may promote or inhibit cell death. Surprisingly, although we know that, at its core, autophagy involves degradation of sequestered cytoplasmic material, and therefore presumably must be mediating its effects on cell death by degrading something, in most cases we have little idea of what is being degraded to promote autophagy's pro- or anti-death activities. Because autophagy is known to play important roles in health and many diseases, it is critical to understand the mechanisms by which autophagy interacts with and affects the cell death machinery since this will perhaps allow new ways to prevent or treat disease. In the present chapter, we discuss the current state of understanding of these processes.
自噬与真核细胞死亡和细胞凋亡密切相关。事实上,在某些情况下,相同的蛋白质可以同时控制自噬和细胞凋亡。凋亡信号可以调节自噬,反之亦然,自噬可以调节细胞凋亡(很可能还有其他细胞死亡机制)。然而,自噬和细胞死亡之间的分子联系很复杂,在不同的情况下,自噬可能促进或抑制细胞死亡。令人惊讶的是,尽管我们知道自噬的核心过程涉及隔离细胞质物质的降解,因此自噬可能通过降解某些物质来介导其对细胞死亡的影响,但在大多数情况下,我们对促进自噬促进或抑制细胞死亡的降解物知之甚少。由于自噬在健康和许多疾病中发挥着重要作用,因此了解自噬与细胞死亡机制相互作用的机制至关重要,因为这可能为预防或治疗疾病提供新的方法。在本章中,我们讨论了对这些过程的当前理解状态。