National Center for Drug Research and Evaluation, National Institute of Health, Viale Regina Elena, 00161 Rome, Italy.
Department of Precision Medicine, University of Campania "Luigi Vanvitelli", 80138 Naples, Italy.
Int J Mol Sci. 2019 Feb 8;20(3):725. doi: 10.3390/ijms20030725.
Autophagy is an evolutionarily conserved cellular process, through which damaged organelles and superfluous proteins are degraded, for maintaining the correct cellular balance during stress insult. It involves formation of double-membrane vesicles, named autophagosomes, that capture cytosolic cargo and deliver it to lysosomes, where the breakdown products are recycled back to cytoplasm. On the basis of degraded cell components, some selective types of autophagy can be identified (mitophagy, ribophagy, reticulophagy, lysophagy, pexophagy, lipophagy, and glycophagy). Dysregulation of autophagy can induce various disease manifestations, such as inflammation, aging, metabolic diseases, neurodegenerative disorders and cancer. The understanding of the molecular mechanism that regulates the different phases of the autophagic process and the role in the development of diseases are only in an early stage. There are still questions that must be answered concerning the functions of the autophagy-related proteins. In this review, we describe the principal cellular and molecular autophagic functions, selective types of autophagy and the main in vitro methods to detect the role of autophagy in the cellular physiology. We also summarize the importance of the autophagic behavior in some diseases to provide a novel insight for target therapies.
自噬是一种进化上保守的细胞过程,通过该过程,受损的细胞器和多余的蛋白质被降解,从而在应激损伤时维持细胞内的平衡。它涉及到双层膜囊泡(自噬体)的形成,这些囊泡可以捕获细胞质中的货物,并将其运送到溶酶体中,在那里,降解产物被回收回细胞质中。根据降解的细胞成分,可以识别出一些选择性的自噬类型(线粒体自噬、核糖体自噬、内质网自噬、溶酶体自噬、过氧化物酶体自噬、脂自噬和糖自噬)。自噬的失调会导致各种疾病表现,如炎症、衰老、代谢疾病、神经退行性疾病和癌症。对调节自噬过程不同阶段的分子机制及其在疾病发展中的作用的理解还处于早期阶段。关于自噬相关蛋白的功能,仍有许多问题亟待解答。在这篇综述中,我们描述了主要的细胞和分子自噬功能、选择性的自噬类型以及检测自噬在细胞生理学中作用的主要体外方法。我们还总结了自噬行为在某些疾病中的重要性,为靶向治疗提供了新的见解。