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- Title
ANKFY1 bridges ATG2A-mediated lipid transfer from endosomes to phagophores.
- Authors
Wei, Bin; Fu, Yuhui; Li, Xiuzhi; Chen, Fang; Zhang, Yiqing; Chen, Hanmo; Tong, Mindan; Li, Linsen; Pan, Yi; Zhang, Shen; Chen, She; Liu, Xiaoxia; Zhong, Qing
- Abstract
Macroautophagy is a process that cells engulf cytosolic materials by autophagosomes and deliver them to lysosomes for degradation. The biogenesis of autophagosomes requires ATG2 as a lipid transfer protein to transport lipids from existing membranes to phagophores. It is generally believed that endoplasmic reticulum is the main source for lipid supply of the forming autophagosomes; whether ATG2 can transfer lipids from other organelles to phagophores remains elusive. In this study, we identified a new ATG2A-binding protein, ANKFY1. Depletion of this endosome-localized protein led to the impaired autophagosome growth and the reduced autophagy flux, which largely phenocopied ATG2A/B depletion. A pool of ANKFY1 co-localized with ATG2A between endosomes and phagophores and depletion of UVRAG, ANKFY1 or ATG2A/B led to reduction of PI3P distribution on phagophores. Purified recombinant ANKFY1 bound to PI3P on membrane through its FYVE domain and enhanced ATG2A-mediated lipid transfer between PI3P-containing liposomes. Therefore, we propose that ANKFY1 recruits ATG2A to PI3P-enriched endosomes and promotes ATG2A-mediated lipid transfer from endosomes to phagophores. This finding implicates a new lipid source for ATG2A-mediated phagophore expansion, where endosomes donate PI3P and other lipids to phagophores via lipid transfer.
- Subjects
ENDOSOMES; LIPID transfer protein; ENDOPLASMIC reticulum; LYSOSOMES; AUTOPHAGY; LIPIDS
- Publication
Cell Discovery, 2024, Vol 10, Issue 1, p1
- ISSN
2056-5968
- Publication type
Article
- DOI
10.1038/s41421-024-00659-y