Cancer Research UK Edinburgh Centre, Institute of Genetics and Molecular Medicine, University of Edinburgh, UK.
FEBS J. 2020 Nov;287(22):4806-4821. doi: 10.1111/febs.15334. Epub 2020 May 1.
Autophagosomes are vital organelles required to facilitate the lysosomal degradation of cytoplasmic cargo, thereby playing an important role in maintaining cellular homeostasis. A number of autophagy-related (ATG) protein complexes are recruited to the site of autophagosome biogenesis where they act to facilitate membrane growth and maturation. Regulated recruitment of ATG complexes to autophagosomal membranes is essential for their autophagic activities and is required to ensure the efficient engulfment of cargo destined for lysosomal degradation. In this review, we discuss our current understanding of the spatiotemporal hierarchy between ATG proteins, examining the mechanisms underlying their recruitment to membranes. A particular focus is placed on the relevance of phosphatidylinositol 3-phosphate and the extent to which the core autophagy players are reliant on this lipid for their localisation to autophagic membranes. In addition, open questions and potential future research directions regarding the membrane recruitment and displacement of ATG proteins are discussed here.
自噬体是促进细胞质货物溶酶体降解所必需的重要细胞器,因此在维持细胞内稳态方面发挥着重要作用。许多自噬相关(ATG)蛋白复合物被招募到自噬体生物发生的部位,在那里它们促进膜的生长和成熟。ATG 复合物在自噬体膜上的受调控募集对于它们的自噬活性是必不可少的,并且需要确保有效吞噬用于溶酶体降解的货物。在这篇综述中,我们讨论了我们对 ATG 蛋白之间的时空层次结构的现有理解,研究了它们在膜上募集的机制。特别关注的是磷脂酰肌醇 3-磷酸的相关性以及核心自噬因子在多大程度上依赖于这种脂质将其定位于自噬体膜上。此外,还讨论了关于 ATG 蛋白的膜募集和置换的悬而未决的问题和潜在的未来研究方向。