MOSPD3 mediates the ER recruitment of ATG2A to promote autophagy

Original paper: https://rupress.org/jcb/article/225/1... PRESENTERS: Tiantian Zhou and Yazhou Liu, on behalf of the co-first authors Yuanjiao Du, Tiantian Zhou and Yazhou Liu. Cells survive stress by digesting and recycling their own worn-out parts, a process called autophagy. It begins when a cup-shaped membrane sac, the phagophore, grows and closes around the material to be cleared. Building that sac takes a large amount of lipid, and the lipid is piped in from the cell's membrane factory, the endoplasmic reticulum, by a long bridge-shaped protein called ATG2A. Researchers already knew what holds the phagophore end of this bridge in place. The endoplasmic reticulum end was unknown. This video shows how the authors found that missing attachment point. Working in cells where the natural gene was tagged rather than artificially overproduced, and combining live imaging with a technique that overlays fluorescence onto electron microscopy images, they show that a small endoplasmic reticulum protein, MOSPD3, collects at exactly the sites where new phagophores are forming. MOSPD3 holds ATG2A there by gripping one short segment near the start of the ATG2A protein. When that grip is broken, either by deleting the gripping module of MOSPD3 or by changing a single amino acid in the segment it grips, ATG2A no longer reaches the endoplasmic reticulum and the cell can no longer complete autophagy efficiently. A closely related protein, MOSPD1, performs the same job for ATG2A's counterpart, ATG2B. KEYWORDS autophagy; autophagosome biogenesis; phagophore; lipid transfer protein; membrane contact site; endoplasmic reticulum; ATG2A; ATG2B; MOSPD3; MOSPD1; VAP family; MSP domain; FFNT motif; autophagic flux; FIP200; DFCP1; LC3B; endogenous knock-in; correlative light and electron microscopy