Membrane lipid metabolism at the mitotic exit

MOSCOSO VERÓNICA; RODRIGUEZ SAWICKI LUCIANA; SCAGLIA NATALIA; CÓRSICO BETINA

Whistler

Congreso; Keystone Symposia: Tumor Metabolism: Mechanisms and Targets; 2017

Cell division ends with the reassemble of the nuclear envelope and the separation of the two daughter cells, process that requires dynamic changes in membrane phospholipids. We have previously found that lysophospholipid levels decrease drastically from G2/M to G1 phase, while phosphatidylcholine synthesis increases, suggesting an enhanced membrane production concomitant with a decrease in its turnover. In addition, de novo fatty acid synthesis and incorporation into membranes increases upon cell division (Scaglia, 2014). Thus, we studied the cellular fate of phospholipids synthesized during G2/M and the lipid requirements for cell cycle completion.We synchronized HeLa cells to study lipid synthesis during G2/M. Metabolic labeling with 14C-acetate and the subsequent separation of subcellular fractions using a sucrose gradient allowed us to determine the distribution of incorporated label into lipids during cell division. We also used the choline analog propargylcholine, and the coupled click-chemistry reaction, to assess the fate of newly synthesized phosphatidylcholine in G2/M. Both approaches showed that lipids synthesized during G2/M localized in a region compatible with the nucleus and endoplasmic reticulum, suggesting that newly synthesized membrane is used for nuclear envelope reassembly. Notably, impairment of fatty acid synthesis or Lysophospholipids reacylation induced cell cycle arrest whereas knockdown of CTα, the rate-limiting enzyme of phosphatidylcholine synthesis, had no effect on proliferation.These studies contribute to the knowledge of the metabolic requirements during the cell cycle and could have implications for the treatment of hyperproliferative diseases.