Phospholipid scramblase involved in autophagy by mediating autophagosomal membrane expansion (   , ). Cycles between the preautophagosomal structure/phagophore assembly site (PAS) and the cytoplasmic vesicle pool and supplies membrane for the growing autophagosome ( ). Lipid scramblase activity plays a key role in preautophagosomal structure/phagophore assembly by distributing the phospholipids that arrive through ATG2 (ATG2A or ATG2B) from the cytoplasmic to the luminal leaflet of the bilayer, thereby driving autophagosomal membrane expansion . Also required to supply phosphatidylinositol 4-phosphate to the autophagosome initiation site by recruiting the phosphatidylinositol 4-kinase beta (PI4KB) in a process dependent on ARFIP2, but not ARFIP1 . In addition to autophagy, also plays a role in necrotic cell death (By similarity).
Subcellular locations: Preautophagosomal structure membrane, Cytoplasmic vesicle, Autophagosome membrane, Golgi apparatus, Trans-Golgi network membrane, Late endosome membrane, Recycling endosome membrane, Endoplasmic reticulum membrane, Mitochondrion membrane
Mainly localizes to the trans-Golgi network (TGN) and the endosomal system; cycles between them though vesicle trafficking (, ). Export from the TGN to promote formation of autophagosomes is mediated by the AP-4 complex (, ). Under amino acid starvation or rapamycin treatment, redistributes to preautophagosomal structure/phagophore assembly site (PAS) . The starvation-induced redistribution depends on ULK1, ATG13, as well as SH3GLB1 . Upon autophagy induction, a small portion transiently localizes to the autophagic membranes . Recruited to damaged mitochondria during mitophagy in a RIMOC1-dependent manner .