Toward a standard model for autophagosome biogenesis

Abstract

Two papers in this issue resolve a long-standing obstacle to a "standard model" for autophagosome biogenesis in mammals. The first, Olivas et al. (2023. J. Cell Biol. https://doi.org/10.1083/jcb.202208088), uses biochemistry to confirm that the lipid scramblase ATG9A is a bona fide autophagosome component, while the second, Broadbent et al. (2023. J. Cell Biol. https://doi.org/10.1083/jcb.202210078), uses particle tracking to show that the dynamics of autophagy proteins are consistent with the concept.

Figure 1.

ATG2 tethering slows diffusion of the ATG9A vesicle seeds of autophagosomes. (a) Schematic of an untethered ATG9 vesicle prior to ATG2 recruitment. The dashed lines indicate the higher diffusivity random walk that ATG9 vesicles and other autophagy proteins undergo prior to ATG2 recruitment. (b) A phagophore following ATG2 recruitment. The stabilization of ATG9 vesicles at ER contact sites causes a dramatic reduction of diffusivity and allows for productive ATG2-mediated phagophore expansion.