Centre for Cancer Cell Reprogramming, Faculty of Medicine, University of Oslo, Montebello, N-0379 Oslo, Norway.
Department of Molecular Cell Biology, Institute for Cancer Research, Oslo University Hospital, Montebello, N-0379 Oslo, Norway.
Cells. 2023 Feb 20;12(4):668. doi: 10.3390/cells12040668.
Autophagy-the lysosomal degradation of cytoplasm-plays a central role in cellular homeostasis and protects cells from potentially harmful agents that may accumulate in the cytoplasm, including pathogens, protein aggregates, and dysfunctional organelles. This process is initiated by the formation of a phagophore membrane, which wraps around a portion of cytoplasm or cargo and closes to form a double-membrane autophagosome. Upon the fusion of the autophagosome with a lysosome, the sequestered material is degraded by lysosomal hydrolases in the resulting autolysosome. Several alternative membrane sources of autophagosomes have been proposed, including the plasma membrane, endosomes, mitochondria, endoplasmic reticulum, lipid droplets, hybrid organelles, and de novo synthesis. Here, we review recent progress in our understanding of how the autophagosome is formed and highlight the proposed role of vesicles that contain the lipid scramblase ATG9 as potential seeds for phagophore biogenesis. We also discuss how the phagophore is sealed by the action of the endosomal sorting complex required for transport (ESCRT) proteins.
自噬——溶酶体降解细胞质——在细胞稳态中起着核心作用，并保护细胞免受可能在细胞质中积累的潜在有害因子的侵害，包括病原体、蛋白质聚集体和功能失调的细胞器。这个过程是由吞噬体膜的形成引发的，吞噬体膜围绕细胞质或货物的一部分形成，并闭合形成双层膜自噬体。自噬体与溶酶体融合后，被隔离的物质被溶酶体中的水解酶在形成的自溶体中降解。已经提出了几种自噬体的替代膜来源，包括质膜、内体、线粒体、内质网、脂滴、杂交细胞器和从头合成。在这里，我们回顾了我们对自噬体形成的理解的最新进展，并强调了含有脂质翻转酶 ATG9 的囊泡作为吞噬体生物发生的潜在种子的作用。我们还讨论了吞噬体如何通过内体分选复合物必需的运输 (ESCRT) 蛋白的作用被封闭。
