ATG16L1 induces the formation of phagophore-like membrane cups

Lien vers Pubmed [PMID] – 38834913

Lien vers HAL – hal-04611251

Lien DOI – 10.1038/s41594-024-01300-y

Nat Struct Mol Biol 2024 Sep; 31(9): 1448-1459

The hallmark of non-selective autophagy is the formation of cup-shapedphagophores that capture bulk cytoplasm. The process is accompaniedby the conjugation of LC3B to phagophores by an E3 ligase complexcomprising ATG12–ATG5 and ATG16L1. Here we combined twocomplementary reconstitution approaches to reveal the function of LC3Band its ligase complex during phagophore expansion. We found thatLC3B forms together with ATG12–ATG5–ATG16L1 a membrane coat thatremodels flat membranes into cups that closely resemble phagophores.Mechanistically, we revealed that cup formation strictly depends on aclose collaboration between LC3B and ATG16L1. Moreover, only LC3B, butno other member of the ATG8 protein family, promotes cup formation.ATG16L1 truncates that lacked the C-terminal membrane binding domaincatalyzed LC3B lipidation but failed to assemble coats, did not promote cupformation and inhibited the biogenesis of non-selective autophagosomes.Our results thus demonstrate that ATG16L1 and LC3B induce and stabilizethe characteristic cup-like shape of phagophores.