Cell cycle arrest induces lipid droplet formation and confers ferroptosis resistance

How cells coordinate cell cycling with cell survival and death remains incompletely understood. Here, we show that cell cycle arrest has a potent suppressive effect on ferroptosis, a form of regulated cell death induced by overwhelming lipid peroxidation at cellular membranes. Mechanistically, cell cycle arrest induces diacylglycerol acyltransferase (DGAT)-dependent lipid droplet formation to sequester excessive polyunsaturated fatty acids (PUFAs) that accumulate in arrested cells in triacylglycerols (TAGs), resulting in ferroptosis suppression. Consequently, DGAT inhibition orchestrates a reshuffling of PUFAs from TAGs to phospholipids and re-sensitizes arrested cells to ferroptosis. We show that some…

• CP
  Cancer Prevention and Research Institute of Texas

  Award: RP230072
• EC
  Emerson Collective
• NI
  National Institutes of Health

  Awards: P30CA016672, R01CA247992, R01CA269646, R01CA181196, R01CA244144, RP230072
• UO
  University of Texas MD Anderson Cancer Center

  Awards: P30CA016672, RP230072
• NC
  National Cancer Institute

  Awards: R01CA181196, R01CA244144, R01CA247992, U54 CA274220, R01CA269646