HS1BP3 provides a novel mechanism of negative autophagy regulation through membrane lipids.

The formation and maturation of the autophagosome, a morphological hallmark of macroautophagy/autophagy, is tightly controlled with regard to location, timing and intensity. Various proteins have been characterized to be essential in regulating autophagosome biogenesis, whereas little is known about the roles of specific lipids and their metabolizing enzymes in this process. In a recent paper, Holland et al. identified the phosphoinositide-binding protein HS1BP3 as a novel negative regulator of autophagosome formation. HS1BP3 is proposed to act by inhibiting PLD1 (phospholipase D1) activity and localization to ATG16L1 and TFRC (transferrin receptor)-positive vesicles thereby modulating the phosphatidic acid (PA) levels and lipid composition of autophagosome precursor membranes.