London Research Institute, Cancer Research UK, London, UK.
Autophagy. 2012 Sep;8(9):1397-400. doi: 10.4161/auto.21043. Epub 2012 Jun 21.
Autophagy is a conserved and highly regulated catabolic pathway, transferring cytoplasmic components in autophagosomes to lysosomes for degradation and providing amino acids during starvation. In multicellular organisms autophagy plays an important role for tissue homeostasis, and deregulation of autophagy has been implicated in a broad range of diseases, including cancer and neurodegenerative disorders. In mammals, many aspects of autophagy still need to be fully elucidated: what is the exact hierarchy and relationship between ATG proteins and other factors that lead to the formation and expansion of phagophores? Where does the membrane source for autophagosome formation originate? Which signaling events trigger amino acid starvation-induced autophagy? How are the activities of ULK1/2 and the class III PtdIns3K regulated and linked to each other? To develop therapeutic strategies to manipulate autophagy in human disease, a comprehensive understanding of the molecular protein machinery mediating and regulating autophagy is required.
自噬是一种保守且高度调控的分解代谢途径，通过自噬体将细胞质成分转移到溶酶体中进行降解，并在饥饿时提供氨基酸。在多细胞生物中，自噬对于组织稳态起着重要作用，自噬的失调与广泛的疾病有关，包括癌症和神经退行性疾病。在哺乳动物中，自噬的许多方面仍需要充分阐明：导致吞噬体形成和扩张的 ATG 蛋白和其他因素之间的确切层次结构和关系是什么？形成自噬体的膜源来自何处？哪些信号事件触发氨基酸饥饿诱导的自噬？ULK1/2 和 III 类 PtdIns3K 的活性如何被调节并相互关联？为了开发在人类疾病中操纵自噬的治疗策略，需要全面了解介导和调节自噬的分子蛋白机制。
