Triacylglycerols (TAGs), a family of neutral lipids, are known as energy storage molecules. They contain three fatty acyl chains, which vary in chain length and unsaturation states, resulting in many chemically diverse TAG species. Their structure-dependent regulation as well as functional roles in different biological events has started to gain more attention. Our global lipidomics study revealed the accumulation of PUFA-TAGs, TAGs containing polyunsaturated fatty acyl chains, as the majority of the changes in the lipidome during apoptosis. These accumulations are caused by activated diacylglycerol acyltransferases, which could be the downstream target of p53 activation during apoptosis. PUFA-TAG accumulation was then found as a general phenomenon that occur in apoptosis independent of cytotoxic agents and cell lines, and these accumulated species are stored within lipid droplets. The compositional and spatial regulation of PUFA-TAGs suggests their functional involvement in apoptosis. Specifically, unsaturated lipids are recruited to TAGs in lipid droplets, “away” from membrane phospholipids to protect cells from lipid peroxidation induced membrane damage during apoptosis. Indeed, the incorporation of polyunsaturated fatty acid into membrane phospholipids rendered cells more sensitive to oxidative stress induced cell death, supporting the protective role of PUFA-TAGs. Overall, we envision that PUFA-TAG accumulation might be a biomarker of apoptosis, and inhibiting TAG biosynthesis could be a potential strategy to improve cell death induced by cytotoxic agents.

Triacylglycerols play a protective role during apoptosis

255th National Meeting (2018)

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