Toward an understanding of autophagosome-lysosome fusion: The unsuspected role of ATG14.
Although largely overlooked relative to the process of phagophore formation, the mechanism through which autophagosomes fuse with lysosomes is a critical aspect of macroautophagy that is not fully understood. In particular, this step must be carefully regulated to prevent premature fusion of an incomplete autophagosome (that is, a phagophore) with a lysosome, because such an event would not allow access of the partially sequestered cargo to the lysosome lumen. The identification of the autophagosome-associated SNARE protein STX17 (syntaxin 17) provided some clue in the understanding of this process. STX17 is recruited specifically to mature autophagosomes, and functions in mediating autophagosome-lysosome fusion by forming a complex with the Qbc SNARE SNAP29 and the lysosomal R-SNARE VAMP8. Additionally, STX17 plays a role in the early events of autophagy by interacting with the phosphatidylinositol 3-kinase complex component ATG14. Upon autophagy induction STX17 is strictly required for ATG14 recruitment to the ER-mitochondria contact sites, a critical step for the assembly of the phagophore and therefore for autophagosome formation. In their recent paper, Diao and collaborators now show that the ATG14-STX17-SNAP29 interaction mediates autophagosome-lysosome tethering and fusion events, thus revealing a novel function of ATG14 in the later steps of the autophagy pathway.
a Life Sciences Institute; University of Michigan ; Ann Arbor , MI USA.
Amélie
A
Bernard
Daniel J
DJ
Klionsky
D000818:Animals; D001343:Autophagy / Q000502:physiology*; D006801:Humans; D008247:Lysosomes / Q000378:metabolism*; D008561:Membrane Fusion / Q000502:physiology*; D010588:Phagosomes / Q000378:metabolism; D050600:SNARE Proteins / Q000378:metabolism*
D050600:SNARE Proteins
SNARE; autophagy; fusion; lysosome; stress