Autophagosome Biogenesis

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...

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Main Authors: Yan Zhen, Harald Stenmark
Format: Article
Language:English
Published: MDPI AG 2023-02-01
Series:Cells
Subjects:
Online Access:https://www.mdpi.com/2073-4409/12/4/668
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author Yan Zhen
Harald Stenmark
author_facet Yan Zhen
Harald Stenmark
author_sort Yan Zhen
collection DOAJ
description 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.
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spelling doaj.art-0887ba62ad354b549a6f0a44f4da887e2023-11-16T19:45:35ZengMDPI AGCells2073-44092023-02-0112466810.3390/cells12040668Autophagosome BiogenesisYan Zhen0Harald Stenmark1Centre for Cancer Cell Reprogramming, Faculty of Medicine, University of Oslo, Montebello, N-0379 Oslo, NorwayCentre for Cancer Cell Reprogramming, Faculty of Medicine, University of Oslo, Montebello, N-0379 Oslo, NorwayAutophagy–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.https://www.mdpi.com/2073-4409/12/4/668autophagyautophagosomeendosomeESCRTlipid transportlysosome
spellingShingle Yan Zhen
Harald Stenmark
Autophagosome Biogenesis
Cells
autophagy
autophagosome
endosome
ESCRT
lipid transport
lysosome
title Autophagosome Biogenesis
title_full Autophagosome Biogenesis
title_fullStr Autophagosome Biogenesis
title_full_unstemmed Autophagosome Biogenesis
title_short Autophagosome Biogenesis
title_sort autophagosome biogenesis
topic autophagy
autophagosome
endosome
ESCRT
lipid transport
lysosome
url https://www.mdpi.com/2073-4409/12/4/668
work_keys_str_mv AT yanzhen autophagosomebiogenesis
AT haraldstenmark autophagosomebiogenesis