Int J Mol Sci 2026 May 28;2711:. doi: 10.3390/ijms27114859.

Perilipin 2 Stabilizes Lipid Droplets and Coordinates Mitochondrial Fatty Acid Flux and ER Stress Adaptation in Apostichopus japonicus.

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Perilipins (PLINs) are lipid droplet-associated proteins that regulate lipid storage, mobilization, and metabolism, yet their roles in invertebrates remain poorly characterized. This study aimed to investigate the evolutionary conservation and functional adaptation of PLIN2 in the sea cucumber Apostichopus japonicus. Phylogenetic analysis placed A. japonicus PLIN2 within the PLIN2 clade, forming an echinoderm-specific branch distinct from vertebrate PLIN2s. Structural prediction revealed an N-terminal PAT domain containing an amphipathic helix that was required for lipid droplet targeting, as deletion of this region abolished its localization to lipid droplet. Functionally, PLIN2 abundance positively correlated with lipid droplet formation, and its knockdown reduced triacylglycerol accumulation while upregulating lipolysis-related genes. Pull-down and co-immunoprecipitation assays identified interactions between PLIN2 and the endoplasmic reticulum protein ERP44, as well as the mitochondrial protein TRXR2, suggesting a role in lipid droplet-organelle coupling. Consistently, disruption of the PLIN2-TRXR2 module impaired fatty acid transfer from lipid droplets to mitochondria, leading to suppressed β-oxidation and decreased ATP production. In addition, PLIN2 mediates the protective role of lipid droplets against Vibrio splendidus-induced ER stress. Together, these findings establish A. japonicus PLIN2 as a multifunctional lipid droplet-associated protein that coordinates lipid droplet stability with organelle communication, energy metabolism, and ER homeostasis.

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