Small GTPases controlling autophagy-related membrane traffic in yeast and metazoans

Abstract

During macroautophagy, the phagophore-mediated formation of autophagosomes and their subsequent fusion with lysosomes requires extensive transformation of the endomembrane system. Membrane dynamics in eukaryotic cells is regulated by small GTPase proteins including Arfs and Rabs. The small GTPase proteins that regulate autophagic membrane traffic are mostly conserved in yeast and metazoans, but there are also several differences. In this mini-review, we compare the small GTPase network of yeast and metazoan cells that regulates autophagy, and point out the similarities and differences in these organisms.

Keywords: Arf; Rab; Rag; TORC1; autolysosome; autophagosome; autophagy; membrane fusion; membrane trafficking.

Figure 1.

Small GTPases integrate autophagy into the membrane trafficking network. Key trafficking routes related to autophagy and their regulatory small GTPases in mammalian cells are depicted in this figure. Regulation of autophagy can be divided into 4 main steps. (1) Induction of autophagy. Autophagy is suppressed by TORC1, which is activated by Rheb during its transient recruitment to lysosomes by Rags. TORC1 activity is also regulated by Arl8 dependent lysosomal positioning. (2) Autophagosome formation. The Sar1 and Rab1 dependent early secretory and Rab11 dependent endosomal recycling pathways contribute to the delivery of membrane and Atg proteins to the PAS. (3) Autophagosome-lysosome fusion. The fusion of autophagosomes with late endosomes and lysosomes requires Rab7. The Rab21 dependent relocalization of Vamp7/8 from endosomes to lysosomes is also necessary for efficient fusion. (4) Autolysosomal degradation. The degradative capacity of autolysosomes depends on Rab5- and possibly Rab24-dependent biosynthetic transport. AL: Autolysosome, AP: Autophagosome, EE: Early endosome, GO: Golgi, LE/L: Late endosome/Lysosome, PH: Phagophore, RE: Recycling endosome, SG: Secretory granule.