Abstract
In our recent paper, we biochemically analyzed autophagosome-related membranes at the initiation stage of macroautophagy/autophagy using atg knockout (KO) cells and demonstrated that the ULK complex is recruited to 2 distinct membranes: the ER membrane and ATG9A-positive autophagosome precursors. We have also identified phosphatidylinositol synthase (PIS)-enriched ER subdomains as the initiation site of autophagosome formation. Based on these findings, we propose that the ULK complex, the PIS-enriched ER subdomain, and ATG9A vesicles together initiate autophagosome formation.
Keywords:
ATG9A; RB1CC1; ULK complex; autophagy; phosphatidylinositol synthase.
MeSH terms
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Adaptor Proteins, Signal Transducing / metabolism
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Adaptor Proteins, Signal Transducing / physiology
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Animals
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Autophagosomes / physiology*
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Autophagy-Related Protein-1 Homolog / metabolism*
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Autophagy-Related Protein-1 Homolog / physiology
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Autophagy-Related Proteins / metabolism
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Autophagy-Related Proteins / physiology
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CDP-Diacylglycerol-Inositol 3-Phosphatidyltransferase / metabolism*
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Cells, Cultured
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Endoplasmic Reticulum / chemistry
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Endoplasmic Reticulum / enzymology
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Endoplasmic Reticulum / metabolism*
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Gene Knockdown Techniques
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Humans
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Membrane Microdomains / chemistry
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Membrane Microdomains / enzymology
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Membrane Microdomains / metabolism*
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Multiprotein Complexes / physiology*
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Protein-Tyrosine Kinases / metabolism
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Protein-Tyrosine Kinases / physiology
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Vesicular Transport Proteins / metabolism
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Vesicular Transport Proteins / physiology
Substances
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ATG13 protein, human
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Adaptor Proteins, Signal Transducing
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ATG101 protein, human
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Autophagy-Related Proteins
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Multiprotein Complexes
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RB1CC1 protein, human
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Vesicular Transport Proteins
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Protein-Tyrosine Kinases
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Autophagy-Related Protein-1 Homolog
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CDP-Diacylglycerol-Inositol 3-Phosphatidyltransferase