Cellular trafficking and membrane protein dynamics rely on curvature stress induced by non-bilayer phospholipids within cell membranes. While membrane fluidity has been shown to be maintained by homeoviscous adaptation through phospholipid metabolism, little is understood about the regulation of lipid spontaneous curvature. Based on the report of non-bilayer lipid enrichment in ctenophore membranes from deep-ocean environments, we have employed hydrostatic pressure as a synthetic inhibitor of lipid curvature to investigate homeocurvature regulation in model cells. Constraining lipidome curvature by lowering the phosphatidylethanolamine (PE) to phosphatidylcholine (PC) ratio in yeast compromised growth and viability under pressure. X-ray scattering of pressure-grown yeast lipid extracts revealed enhanced non-lamellar phase formation, which coincided with increased phosphatidylinositol (PI)—the only major phospholipid class with an uncharacterized spontaneous curvature. We report that PI is a non-bilayer phospholipid with negative spontaneous curvature, intermediate between PE and PC, and sufficient to enable vesicle fusion when substituted for PE. Incorporating PI into lipidome curvature estimation buffered mean curvature in two distantly related yeast species. Furthermore, in a human cancer cell line, we found ether lipid metabolism to similarly buffer mean lipidome curvature. Together, these findings point to eukaryotic mechanisms that maintain membrane curvature within a viable range to meet the physiological needs of cells.
Milshteyn et al. (Sun,) studied this question.