ER-localized phosphatidylethanolamine synthase plays a conserved role in lipid droplet formation

Abstract

AbstractThe asymmetric distribution of phospholipids in membranes is a fundamental principle of cellular compartmentalization and organization. Phosphatidylethanolamine (PE), a nonbilayer phospholipid that contributes to organelle shape and function, is synthesized at several subcellular localizations via semi-redundant pathways. Previously, we demonstrated in the yeast Saccharomyces cerevisiae that the PE synthase Psd1, which primarily operates on the mitochondrial inner membrane, is additionally targeted to the endoplasmic reticulum (ER). While ER-localized Psd1 is required to support cellular growth in the absence of redundant pathways, its physiological function at the ER is unclear. We now demonstrate that ER-localized Psd1 sub-localizes on the ER to lipid droplet (LD) attachment sites and further show it is specifically required for normal LD formation. We also find that the role of PSD enzymes in LD formation is conserved in other organisms. Thus, we have identified PSD enzymes as novel regulators of LDs and demonstrate that both mitochondria and LDs in yeast are organized and shaped by the spatial positioning of a single PE synthesis enzyme.