ATG2A connects lipid droplets and the ER to regulate lipid storage

The endoplasmic reticulum (ER) must carefully regulate the levels of nonmembrane lipids such as diacylglycerol (DAG), phosphatidic acid (PA), and triacylglycerol (TAG) to maintain membrane integrity and prevent lipotoxic stress. While ATG2A is well known as a lipid transfer protein essential for autophagosome formation, its role at lipid droplet (LD) contact sites has remained unclear. In our recent work, we show that ATG2A functions beyond its typical role in autophagy as a key regulator of lipid storage, transferring DAG, TAG, and PA from the ER to LDs and recruiting the TAG synthesis enzyme DGAT2 to promote LD expansion. Without ATG2A, lipids accumulate in the ER, leading to smaller, more numerous nucleated LDs rather than proper growth. Notably, ATG2A-mediated DAG transfer recruits DGAT2 to LD surfaces, enabling local TAG synthesis that prevents nonmembrane lipid accumulation in the ER. This cooperative process reveals ATG2A's dual role in both autophagy and lipid storage, highlighting an unexpected link between autophagy machinery and lipid storage.