Autophagy is an intracellular degradation system conserved among eukaryotes, which utilizes a double-membrane organelle, an autophagosome, to sequester and deliver cytoplasmic materials to lysosomes for degradation [1]. When autophagy is induced by starvation in budding yeast, Atg proteins undergo phase separation to form the preautophagosomal structure (PAS) [2]. Atg9 is the sole transmembrane protein among core Atg proteins and is embedded in a vesicle termed the Atg9 vesicle at the Golgi apparatus, which targets the PAS and functions as the initial membrane source for autophagosome formation [1]. By unknown mechanisms, Atg9 vesicles transform into a cup-shaped isolation membrane (also known as phagophore), which expands and finally seals into an autophagosome.

For expansion, isolation membranes must receive sufficient amounts of phospholipids from endomembranes as a building block. In budding yeast, the expanding edge of the isolation membrane contacts the endoplasmic reticulum (ER), especially the ER exit site (ERES) [3, 4]. Atg9, together with the Atg2–Atg18 complex, localizes at the edge of the isolation membrane and contacts the ERES, where Atg2 functions as a tether between ERES and the isolation membrane [1, 5]. Recently, in vitro analyses have identified the lipid transfer activity of Atg2 between membranes, which proposed an attractive model that Atg2 functions as a conduit and directly provides phospholipids from the ER to the isolation membrane for expansion [6]. However, this model has several serious shortcomings. One of which is the activity of Atg2 to transfer phospholipids only between the cytoplasmic leaflets of the membrane; Atg2 is not a transmembrane protein and cannot transport a phospholipid across the lipid bilayer membrane. As a result, phospholipids transferred from the ER by Atg2 would accumulate at the cytoplasmic leaflet of the isolation membrane, which must be distributed to the luminal leaflet for membrane expansion. Lipid transport between the two leaflets of a membrane is mediated by transmembrane proteins termed lipid translocases, which are further classified into flippases, floppases, and scramblases [7]. Flippases and floppases transport lipids in a unidirectional manner using ATP, whereas scramblases transport lipids bidirectionally without the help of ATP.

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