Huang Ju, Klionsky Daniel J
University of Michigan, Life Sciences Institute, Department of Molecular, Cellular and Developmental Biology, Ann Arbor, Michigan 48109 , USA.
Cell Cycle. 2007 Aug 1;6(15):1837-49. doi: 10.4161/cc.6.15.4511. Epub 2007 May 25.
As a conserved cellular degradative pathway in eukaryotes, autophagy relieves cells from various types of stress. There are different forms of autophagy, and the ongoing studies of the molecular mechanisms and cellular functions of these processes are unraveling their significant roles in human health. Currently, the best-studied of these pathways is macroautophagy, which is linked to a range of human disease. For example, as part of the host immune defense mechanism, macroautophagy is activated to eliminate invasive pathogenic bacteria; however, in some cases bacteria subvert this process for their own replication. Autophagy also contributes to endogenous major histocompatibility complex class II antigen presentation, reflecting its role in adaptive immunity. In certain neurodegenerative diseases, which are associated with aggregation-prone proteins, macroautophagy plays a protective role in preventing or reducing cytotoxicity by clearance of the toxic proteins; however, the autophagy-dependent processing of some components correlates with the pathogenesis of certain myopathies. Finally, autophagy acts as a mechanism for tumor suppression, although some cancer cells use it as a cytoprotective mechanism. Thus, a fundamental paradox of autophagy is that it can act to promote both cell survival and cell death, depending on the specific conditions.
作为真核生物中一种保守的细胞降解途径,自噬可使细胞从各种类型的应激中解脱出来。自噬有不同的形式,目前对这些过程的分子机制和细胞功能的研究正在揭示它们在人类健康中的重要作用。目前,这些途径中研究得最充分的是巨自噬,它与一系列人类疾病有关。例如,作为宿主免疫防御机制的一部分,巨自噬被激活以清除入侵的致病细菌;然而,在某些情况下,细菌会颠覆这一过程以进行自身复制。自噬也有助于内源性主要组织相容性复合体II类抗原呈递,这反映了它在适应性免疫中的作用。在某些与易聚集蛋白相关的神经退行性疾病中,巨自噬通过清除有毒蛋白在预防或降低细胞毒性方面发挥保护作用;然而,某些成分的自噬依赖性加工与某些肌病的发病机制相关。最后,自噬作为一种肿瘤抑制机制,尽管一些癌细胞将其用作细胞保护机制。因此,自噬的一个基本矛盾在于,根据具体情况,它既可以促进细胞存活,也可以促进细胞死亡。