Previously, our work uncovered a potent autophagy receptor (2014-Cell) and uncovered its oligomerization feature (2017-Nat Cell Biol.). We found PI4P hydrolysis is a lipid quality control mechanism for autophagy (2021-Autophagy); N-terminal acetylation regulates autophagosome fusion (2021-Cell Reports); palmitoylation regulates autophagosome formation (2021-Dev Cell); ER calcium is essential for autophagosome initiation (2023-Nat Comm.). Besides, we also found the tissue/organ specific physiological functions of autophagy. We found that palmitoylation activated autophagy is essential for sperm development (2021-Dev Cell); the inflammation suppression by autophagy in stimulated macrophages (2024-Plos Biol.).
Sphingolipids are ubiquitous components of membranes and function as bioactive lipid signaling molecules. Through genetic screening and lipidomics analyses, we found that the endoplasmic reticulum (ER) calcium channel integrates sphingolipid metabolism with autophagy by regulating ER calcium homeostasis in the yeast Saccharomyces cerevisiae. An ER calcium release channel maintains calcium homeostasis in the ER, which enables normal functioning of the essential sphingolipid synthase. Under starvation conditions, deletion of ER calcium channel causes increases in calcium levels in the ER and then disturbs sphingolipid synthase stability, leading to accumulation of the bioactive sphingolipid, which specifically and completely blocks autophagy and induces loss of starvation resistance in cells. Our findings indicate that calcium homeostasis in the ER mediated by the ER calcium channel translates sphingolipid metabolism into autophagy regulation, further supporting the role of the ER as a signaling hub for calcium homeostasis, sphingolipid metabolism and autophagy.