Telethon Institute of Genetics and Medicine, Pozzuoli, Naples, Italy.
Department of Molecular, Cellular, and Developmental Biology, University of California, Santa Barbara, Santa Barbara, CA, USA.
FEBS Lett. 2019 Nov;593(22):3120-3134. doi: 10.1002/1873-3468.13637. Epub 2019 Oct 21.
Autophagy is widely considered as a housekeeping mechanism that enables cells to survive stress conditions and, in particular, nutrient deprivation. Autophagy begins with the formation of the phagophore that expands and closes around cytosolic material and damaged organelles destined for degradation. The execution of this complex machinery is guaranteed by the coordinated action of more than 40 ATG (autophagy-related) proteins that control the entire process at different stages from the biogenesis of the autophagosome to cargo sequestration and fusion with lysosomes. Autophagosome biogenesis occurs at multiple intracellular sites, such as the endoplasmic reticulum (ER) and the plasma membrane. Soon after the formation of the phagophore, the nascent autophagosome progressively grows in size and ultimately closes by recruiting intracellular membranes. In this review, we focus on the contribution of three membrane sources - the ER, the ER-Golgi intermediate compartment, and the Golgi complex - to autophagosome biogenesis and expansion. We also highlight the interplay between the secretory pathway and autophagy in cells when nutrients are scarce.
自噬被广泛认为是一种细胞自我保护机制，使细胞能够在应激条件下存活，特别是在营养缺乏的情况下。自噬始于吞噬体的形成，吞噬体在细胞质物质和受损细胞器周围扩展并闭合，这些物质和细胞器最终将被降解。这个复杂的机制的执行是由超过 40 种 ATG（自噬相关）蛋白的协调作用来保证的，这些蛋白在自噬体的生物发生、货物隔离以及与溶酶体融合的不同阶段控制着整个过程。自噬体的生物发生发生在多个细胞内部位，如内质网（ER）和质膜。在吞噬体形成后不久，新生的自噬体逐渐增大，最终通过招募细胞内膜而闭合。在这篇综述中，我们重点介绍了三种膜源——内质网、内质网-高尔基体中间区室和高尔基体复合物——对自噬体生物发生和扩展的贡献。我们还强调了在营养物质匮乏时，细胞中分泌途径和自噬之间的相互作用。
