Lipid droplets and polyunsaturated fatty acid trafficking: Balancing life and death

Front Cell Dev Biol. 2023 Jan 27:11:1104725. doi: 10.3389/fcell.2023.1104725. eCollection 2023.

Abstract

Lipid droplets are fat storage organelles ubiquitously distributed across the eukaryotic kingdom. They have a central role in regulating lipid metabolism and undergo a dynamic turnover of biogenesis and breakdown to meet cellular requirements for fatty acids, including polyunsaturated fatty acids. Polyunsaturated fatty acids esterified in membrane phospholipids define membrane fluidity and can be released by the activity of phospholipases A2 to act as ligands for nuclear receptors or to be metabolized into a wide spectrum of lipid signaling mediators. Polyunsaturated fatty acids in membrane phospholipids are also highly susceptible to lipid peroxidation, which if left uncontrolled leads to ferroptotic cell death. On the one hand, lipid droplets act as antioxidant organelles that control polyunsaturated fatty acid storage in triglycerides in order to reduce membrane lipid peroxidation, preserve organelle function and prevent cell death, including ferroptosis. On the other hand, lipid droplet breakdown fine-tunes the delivery of polyunsaturated fatty acids into metabolic and signaling pathways, but unrestricted lipid droplet breakdown may also lead to the release of lethal levels of polyunsaturated fatty acids. Precise regulation of lipid droplet turnover is thus essential for polyunsaturated fatty acid distribution and cellular homeostasis. In this review, we focus on emerging aspects of lipid droplet-mediated regulation of polyunsaturated fatty acid trafficking, including the management of membrane lipid peroxidation, ferroptosis and lipid mediator signaling.

Keywords: fatty acid; ferroptosis; lipid droplet; lipid oxidation; lipolysis; membrane remodeling; phospholipase.

Publication types

  • Review

Grants and funding

This work was supported by the Slovenian Research Agency postdoctoral grants (Z3-2650 to EJ and Z3-3211 to MD), a research programme (P1-0207) and a research project grant (J7-1818) to TP and by the EU COST Action CA19105 EpiLipidNet.