biostudies-literatureChou HYMinistry of Science and Technology, TaiwanAcademia Sinica2750-2765https://www.ebi.ac.uk/biostudies/studies/S-EPMC8526009biostudies-literatureUnknown17(10)Macroautophagy/autophagy is an evolutionarily conserved intracellular pathway for the degradation of cytoplasmic materials. Under stress conditions, autophagy is upregulated and double-membrane autophagosomes are formed by the expansion of phagophores. The ATG16L1 precursor fusion contributes to development of phagophore structures and is critical for the biogenesis of autophagosomes. Here, we discovered a novel role of the protein tyrosine phosphatase PTPN9 in the regulation of homotypic ATG16L1 vesicle fusion and early autophagosome formation. Depletion of PTPN9 and its <i>Drosophila</i> homolog Ptpmeg2 impaired autophagosome formation and autophagic flux. PTPN9 colocalized with ATG16L1 and was essential for homotypic fusion of ATG16L1⁺ vesicles during starvation-induced autopAutophagyPTPN9-mediated dephosphorylation of VTI1B promotes ATG16L1 precursor fusion and autophagosome formation.PMC8526009101CDA-L04MOST108-2311-B-001-014-MY3Lee YTChen GCWen JKHsieh PLLin YJPeng WHChou HYLin SYHung CCfalsePTPN9-mediated dephosphorylation of VTI1B promotes ATG16L1 precursor fusion and autophagosome formation.Macroautophagy/autophagy is an evolutionarily conserved intracellular pathway for the degradation of cytoplasmic materials. Under stress conditions, autophagy is upregulated and double-membrane autophagosomes are formed by the expansion of phagophores. The ATG16L1 precursor fusion contributes to development of phagophore structures and is critical for the biogenesis of autophagosomes. Here, we discovered a novel role of the protein tyrosine phosphatase PTPN9 in the regulation of homotypic ATG16L1 vesicle fusion and early autophagosome formation. Depletion of PTPN9 and its <i>Drosophila</i> homolog Ptpmeg2 impaired autophagosome formation and autophagic flux. PTPN9 colocalized with ATG16L1 and was essential for homotypic fusion of ATG16L1⁺ vesicles during starvation-induced autop2021-01-01T00:00:00Z2021 Oct2025-08-18T09:52:49.597Z2025-04-04T22:42:58.866ZS-EPMC85260093311270510.1080/15548627.2020.1838117