Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
Curr Opin Cell Biol. 2009 Dec;21(6):900-12. doi: 10.1016/j.ceb.2009.08.008. Epub 2009 Sep 24.
Apoptosis ensures quick death and quiet clearance of unwanted or damaged cells, without inducing much, if any, immunological responses from the organism. In metazoan organisms, apoptotic cells are swiftly engulfed by other cells. The degradation of cellular content is initiated in apoptotic cells and completed within engulfing cells. In apoptotic cells, caspase-mediated proteolysis cleaves protein substrates into fragments; nuclear DNA is partially degraded into nucleosomal units; and autophagy potentially contributes to apoptotic cell removal. In engulfing cells, specific signaling pathways promote the sequential fusion of intracellular vesicles with phagosomes and lead to the complete degradation of apoptotic cells in an acidic environment. Phagocytic receptors that initiate the engulfment of apoptotic cells play an additional and crucial role in initiating phagosome maturation through activating these signaling pathways. Here we highlight recent discoveries made in invertebrate models and mammalian systems, focusing on the molecular mechanisms that regulate the efficient degradation of apoptotic cells.
细胞凋亡可确保不需要或受损的细胞迅速死亡并被清除,而不会引起机体产生过多(如果有的话)免疫反应。在多细胞生物中,凋亡细胞会被其他细胞迅速吞噬。吞噬细胞会启动凋亡细胞内的细胞内容物降解,并在吞噬细胞内完成降解。在凋亡细胞中,半胱氨酸天冬氨酸蛋白酶(caspase)介导的蛋白水解将蛋白底物切割成片段;核 DNA 部分降解为核小体单位;自噬可能有助于凋亡细胞的清除。在吞噬细胞中,特定的信号通路促进细胞内囊泡与吞噬体的连续融合,并在酸性环境中完全降解凋亡细胞。起始吞噬凋亡细胞的吞噬受体通过激活这些信号通路,在启动吞噬体成熟方面发挥额外的关键作用。在这里,我们重点介绍在无脊椎动物模型和哺乳动物系统中取得的最新发现,这些发现主要集中在调节凋亡细胞有效降解的分子机制上。