{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Thierer JH"],"funding":["European Research Council","NIDDK NIH HHS","NHLBI NIH HHS","NIGMS NIH HHS"],"pagination":["2095"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC10920679"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["15(1)"],"pubmed_abstract":["Vertebrates transport hydrophobic triglycerides through the circulatory system by packaging them within amphipathic particles called Triglyceride-Rich Lipoproteins. Yet, it remains largely unknown how triglycerides are loaded onto these particles. Mutations in Phospholipase A2 group 12B (PLA2G12B) are known to disrupt lipoprotein homeostasis, but its mechanistic role in this process remains unclear. Here we report that PLA2G12B channels lipids within the lumen of the endoplasmic reticulum into nascent lipoproteins. This activity promotes efficient lipid secretion while preventing excess accumulation of intracellular lipids. We characterize the functional domains, subcellular localization, and interacting partners of PLA2G12B, demonstrating that PLA2G12B is calcium-dependent and tightly associated with the membrane of the endoplasmic reticulum. We also detect profound resistance to atherosclerosis in PLA2G12B mutant mice, suggesting an evolutionary tradeoff between triglyceride transport and cardiovascular disease risk. Here we identify PLA2G12B as a key driver of triglyceride incorporation into vertebrate lipoproteins."],"journal":["Nature communications"],"pubmed_title":["Pla2g12b drives expansion of triglyceride-rich lipoproteins."],"pmcid":["PMC10920679"],"funding_grant_id":["R01 DK093399","F31 HL139338","T32 GM141804","951146","R01 HL158054","F31 HL149174","T32 GM007171"],"pubmed_authors":["Busch-Nentwich EM","Hussain MM","Shen MC","Wilson MH","Thierer JH","Morash M","Moll TOC","Malhotra V","Foresti O","Rawls JF","Farber SA","Yadav PK","Mohlke KL"],"additional_accession":[]},"is_claimable":false,"name":"Pla2g12b drives expansion of triglyceride-rich lipoproteins.","description":"Vertebrates transport hydrophobic triglycerides through the circulatory system by packaging them within amphipathic particles called Triglyceride-Rich Lipoproteins. Yet, it remains largely unknown how triglycerides are loaded onto these particles. Mutations in Phospholipase A2 group 12B (PLA2G12B) are known to disrupt lipoprotein homeostasis, but its mechanistic role in this process remains unclear. Here we report that PLA2G12B channels lipids within the lumen of the endoplasmic reticulum into nascent lipoproteins. This activity promotes efficient lipid secretion while preventing excess accumulation of intracellular lipids. We characterize the functional domains, subcellular localization, and interacting partners of PLA2G12B, demonstrating that PLA2G12B is calcium-dependent and tightly associated with the membrane of the endoplasmic reticulum. We also detect profound resistance to atherosclerosis in PLA2G12B mutant mice, suggesting an evolutionary tradeoff between triglyceride transport and cardiovascular disease risk. Here we identify PLA2G12B as a key driver of triglyceride incorporation into vertebrate lipoproteins.","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Mar","modification":"2026-07-09T03:15:56.795Z","creation":"2026-07-09T03:10:16.909Z"},"accession":"S-EPMC10920679","cross_references":{"pubmed":["38453914"],"doi":["10.1038/s41467-024-46102-4"]}}