The autophagic and non-autophagic functions of the

Autophagosome formation depends on PtdIns3P, its presence is deciphered by PROPPINs, a family of β-propellers, which in yeast consists of Atg18, Atg21 and Hsv2 and in mammals of WIPI1, WIPI2, WDR45B/WIPI3 and WDR45/WIPI4. While Atg18 is required for scaffolding the Atg2-Atg9 complex, which mediates non-vesicular membrane transport to the phagophore, Atg21 organizes the Atg8 lipidation machinery. Atg18 further acts as part of a retromer complex in vacuole fragmentation. So far, the function of Hsv2 remained elusive. Here we show that Hsv2 is required for autophagy of large cargos such as the fatty acid synthase complex (FAS) and ribosomes. We further found that Hsv2 interacts with the key retromer component Vps35 and mediates vacuole fission cooperatively with Atg18. Interestingly, the residues for interaction of Hsv2 with Atg2 and Vps35 are distinct from those of Atg18. Hsv2 is known to affect the biogenesis of the spore wall, which prompted us to include diploid cells in our analyses. We found that Hsv2 interacts with the SNARE Pep12, and that Pep12 mislocalized to the vacuole in diploid but not haploid