Lipid droplet biogenesis as a metabolic switch regulating ferroptosis sensitivity in cancer cells

Hanano, Abdulsamie

doi:10.1111/febs.70567

Lipid droplet biogenesis as a metabolic switch regulating ferroptosis sensitivity in cancer cells

2026-04-01

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Hanano, Abdulsamie *

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Amal Yousfan

DOI：10.1111/febs.70567

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Fatty acids (FAs) are essential for cellular growth and homeostasis; however, their excessive accumulation induces lipotoxicity. To prevent FA-induced damage, eukaryotic cells sequester surplus FAs within cytosolic lipid droplets (LDs), dynamic organelles central to lipid storage, metabolism, and signaling. Emerging evidence indicates that LDs suppress ferroptosis, an iron-dependent programmed cell death, by channeling polyunsaturated fatty acids (PUFAs) away from membrane phospholipids, thereby limiting lipid peroxidation. Nonetheless, the molecular mechanisms linking LD biogenesis to ferroptosis susceptibility remain poorly defined. In a recent study published in The FEBS Journal, Kump et al., provided mechanistic insights into how triacylglycerol (TGs) biosynthesis and LD assembly regulate ferroptosis in cancer cells as a function of PUFA availability. Here, we discuss and contextualize their principal findings.

Keywords:

Acyl-CoA diacylglycerol acyltransferase

ferroptosis

lipid droplets

lipid peroxidation

polyunsaturated fatty acids

Lipid droplet biogenesis as a metabolic switch regulating ferroptosis sensitivity in cancer cells

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