Macroautophagy without LC3 conjugation?

Abstract

A recent study makes the surprising observation that autophagosomes can still form in the absence of the core conjugation machinery. Furthermore, while such autophagosomes can fuse with lysosomes, their degradation is delayed, and this is associated with delayed destruction of the inner autophagosomal double membrane, highlighting a new role for proteins thought to act exclusively in the formation of autophagosomes in late stages of the autophagic itinerary within autolysosomes.

Figure 1

IAM route to lysosomal degradation depends on ATG proteins.The function of ATG proteins has been mainly investigated in the context of autophagosome formation. In normal conditions, the IAM of WT cells is sensitive to lysosomal degradation. While autophagic activity is strongly suppressed in ATG conjugation-deficient cells (exemplified by ATG3 KO cells in this Figure), autophagosome-like structures can still form and acquire STX17. These syntaxin17-positive structures are able to fuse with lysosomes. Nevertheless, degradation of the IAM is significantly impaired. These findings reveal a novel function of ATGs with regard to autophagosome maturation steps.