The autophagy protein complex.  The molecular mechanisms of autophagy have been reviewed (Hurley and Young 2017; Dupont et al. 2017). Autophagy is related to apoptosis and autoimmunity (Song et al. 2017; Wu and Adamopoulos 2017).  It is an intracellular degradation process carried out by a double-membrane organelle, termed the autophagosome (Molino et al. 2017). Three proteins (TM9SF1 (TC#8.A.68.1.13), TMEM166 (listed here) and TMEM74 (TC# 9.B.189.2.1)) regulate autophagosome formation (He et al. 2009). The generation of Atg9 vesicles from a Rab11-positive reservoir is tightly controlled by the Bif-1-DNM2 membrane fission machinery in response to cellular demand for autophagy. ATG9A is essential for multiple steps of epithelial tight junction biogenesis and actin cytoskeletal regulation (Dowdell et al. 2020).  Autophagy involves capture of cytoplasmic materials into double-membraned autophagosomes that subsequently fuse with lysosomes for degradation of the materials by lysosomal hydrolases. The cryoelectron microscopy structure of the human ATG9A isoform at 2.9-Å resolution has been solved (Guardia et al. 2020). The structure reveals a fold with a homotrimeric domain-swapped architecture, multiple membrane spans, and a network of branched cavities, consistent with ATG9A being a membrane transporter. Mutational analyses support a role for the cavities in the function of ATG9A. Structure-guided molecular simulations predict that ATG9A causes membrane bending, explaining the localization of this protein to small vesicles and highly curved edges of growing autophagosomes (Guardia et al. 2020). The mechanism of Atg9 recruitment by Atg11 in the cytoplasm-to-vacuole targeting pathway has been examined (Coudevylle et al. 2022). Autophagosomes form de novo, but how is poorly understood. Particularly enigmatic are autophagy-related protein 9 (Atg9)-containing vesicles that are required for autophagy machinery assembly but do not supply the bulk of the autophagosomal membrane. Sawa-Makarska et al. 2020 reconstituted autophagosome nucleation using recombinant components from yeast. They found that Atg9 proteoliposomes first recruited the phosphatidylinositol 3-phosphate kinase complex, followed by Atg21, the Atg2-Atg18 lipid transfer complex, and the E3-like Atg12-Atg5-Atg16 complex, which promoted Atg8 lipidation. They found that Atg2 could transfer lipids for Atg8 lipidation. In selective autophagy, these reactions could potentially be coupled to cargo via Atg19-Atg11-Atg9 interactions. They proposed that Atg9 vesicles form seeds that establish membrane contact sites to initiate lipid transfer from compartments such as the endoplasmic reticulum (Sawa-Makarska et al. 2020). Drosophila Atg9 regulates the actin cytoskeleton via interactions with profilin and Ena (Kiss et al. 2020). RUSC2 and WDR47 oppositely regulate kinesin-1-dependent distribution of ATG9A to the cell periphery (Guardia et al. 2021).  The adaptor protein chaperone AAGAB (TC family 8.A.203) stabilizes AP-4 complex subunits (Mattera et al. 2022).     The cryoelectron microscopy structure of the human ATG9A isoform at 2.9-Å resolution has been solved (Guardia et al. 2020). The structure reveals a fold with a homotrimeric domain-swapped architecture, multiple membrane spans, and a network of branched cavities, consistent with ATG9A being a membrane transporter. Mutational analyses support a role for the cavities in the function of ATG9A. Structure-guided molecular simulations predict that ATG9A causes membrane bending, explaining the localization of this protein to small vesicles and highly curved edges of growing autophagosomes (Guardia et al. 2020). Both GLUT2 and GLUT3 have been expressed in yeast and exhibit most of the characteristics of the proteins expressed in humans (Schmidl et al. 2020).