Abstract
The synthesis and localization of particular lipid species changes throughout the cell cycle.
Major finding: The synthesis and localization of particular lipid species changes throughout the cell cycle.
Concept: Specific lipid species and lipid biosynthetic enzymes are important for successful cell division.
Impact: The specificity of lipid composition in dividing cells suggests that individual lipids have distinct roles.
The lipid composition of membranes can affect both their mechanical properties and the activation of membrane-associated signaling pathways, but the precise cellular roles of most lipids that comprise the vast mammalian lipidome are poorly understood. Atilla-Gokcumen and colleagues hypothesized that a cell's lipid composition may change during the sweeping membrane rearrangements that accompany cell division. Indeed, a liquid-chromatography–mass spectroscopy analysis of global lipid composition in HeLa cells detected 11 lipid species that specifically accumulated during cytokinesis compared with S phase, including sphingolipids and ceramides. Several of the cytokinesis-specific species accumulated in lysates enriched for the midbody, a structure that forms at the interface between dividing cells, and several other lipids that were unchanged throughout the cell cycle specifically accumulated at the midbody during cytokinesis, prompting the authors to investigate the contributions of lipid biosynthetic enzymes to cell division. Of 244 enzymes targeted by RNA interference, knockdown of 23 provoked cytokinesis defects, and 12 were involved in the synthesis of lipids previously identified by the mass spectrometry assay. Analysis of the 3 enzymes with the strongest phenotypes, sphingomyelin phosphodiesterase 4 (SMPD4), galactosylceramidase (GALC), and diacylglycerol O-acyltransferase 2 (DGAT2), showed that their loss affected cellular lipid composition in distinct ways, but that loss of each caused mitotic delay and cell division failure marked by blebbing and distortion, likely reflecting impaired cytoskeletal organization. Together with the observation that membrane stiffness was increased in normal dividing cells, these data suggest that cells may calibrate their lipidome to accommodate the mechanical demands of cell division. The finding that cells regulate levels of particular lipid species during cell division and the identification of lipid biosynthetic enzymes required for cell division set the stage for future investigations into how lipids affect membrane physics, cell signaling, and cytoskeletal organization in dividing cells.
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