Triacylglycerol synthesis and stress response in fission yeast schizosaccharomyces pombe

Abstract

Triacylglycerols (TAG) are important energy storage molecules for nearly all eukaryotic organisms. In this study, we found that two gene products (Plh1p and Dga1p) are responsible for the terminal step of TAG synthesis in the fission yeast Schizosaccharomyces pombe through two different mechanisms: Plh1p is a phospholipid diacylglycerol acyltransferase, localizing to the endoplasmic reticulum, whereas Dga1p is an acyl-CoA:diacylglycerol acyltransferase localizing to the lipid droplets. Cells with both dga1+ and plh1+ deleted (DKO cells) lost viability upon entry into the stationary phase and demonstrated prominent apoptotic markers. Exponentially growing DKO cells also underwent dramatic apoptosis when briefly treated with diacylglycerols (DAGs) high salt or free fatty acids. Moreover, DKO cells have a compromised mating ability upon nutrient starvation. We provide strong evidence suggesting that DAG, not sphingolipids, mediates fatty acid-induced lipoapoptosis in yeast. Lastly, we show that generation of reactive oxygen species is essential to lipoapoptosis. Therefore, we suggest that the TAG biosynthesis in stressful conditions provides a buffering form for highly reactive or toxic molecules such as DAG or ROS. The inhibition of TAG synthesis in fission yeast may generate an endogenous stress environment to the cell, leading to a decreased viability and cell death. Future study should aim at understanding the mechanism by which DAG triggers the apoptotic cell death of DKO cells.