P007
Dividing cells regulate their lipid composition
Eleonora Muro1, G. Ekin Atilla-Gokcumen2,
Josep Relat-Goberna1, Sergi Garcia-Manyes1 and
Ulrike Eggert1
1
King's College London, London, UK
2
Department of Chemistry, The State University of
New York, Buffalo, USA
Massive membrane rearrangements occur during cell division,
however, little is known about specific roles that lipids might play
during this process. Although cells express hundreds of lipid biosynthetic enzymes and thousands of lipids, the biological reasons
for this diversity are not clear. We showed that the lipidome
changes with the cell cycle using LC-MS based lipid profiling.
Dividing cells (mitosis and cytokinesis), compared to S-phase
cells, accumulate 11 lipids with very specific chemical structures,
including their hydrophobic side chains. Using Atomic Force
Microscopy (AFM), we demonstrated in vivo that membranes
of dividing cells have higher mechanical resistance compared
to membranes of nondividing cells. To isolate the mechanical
properties of the lipids, we used an in vitro essay showing
that lipids extracted from dividing cells form stiffer domains,
suggesting structural roles. In parallel, we screened an RNAi
library of lipid biosynthetic enzymes for cytokinesis failure. We
found high correlation between the lipids identified by LC-MS
profiling and knockdown of enzymes predicted to synthesize
these lipid families (Atilla-Gokcumen*, Muro*, et al., Cell 2014).
The phenotypic analysis of selected lipid biosynthetic enzymes
knockdown cells shows primarily an impairment of the cytoskeleton, suggesting cross-talk with membranes. We conclude
that cells actively regulate and modulate their lipid composition
during their division, likely both by stabilizing different membrane
structures and by organizing and transmitting signals.