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LPLAT7 Reutilizes Unsaturated 1-Lysophospholipids Formed During Lysosomal Phospholipid Degradation
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DOI：10.1016/j.jlr.2026.101064.png)
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Abstract
En 中文
Lysosomal phospholipid degradation produces two types of metabolites, either 2-lysophospholipids with saturated fatty acids in sn-1 position or 1-lysophospholipids with unsaturated fatty acids in sn-2 position. They may either be degraded further or re-used for phospholipid synthesis. We found that LPLAT7 (LPGAT1), an acyltransferase of the endoplasmic reticulum, re-acylates specifically lysosome-derived 1-lysophospholipids that carry an unsaturated chain. The enzymatic activity of LPLAT7 was specific for stearoyl-CoA and 1-lyso-2-acyl positional isomers of unsaturated lysophospholipids. In Huh7 cells, Lplat7 knockout prevented the reacylation of 1-lysophospholipids generated by the lysosomal degradation of exogenous 2H-phosphatidylcholine. Inhibition of lysosomal phospholipid degradation reduced the abundance of 1-stearoyl-2-unsaturated PC in Huh7 cells. Lplat7 knockout blunted the loss of unsaturated lysophosphatidylcholine (LPC) in response to lysosomal inhibition, suggesting that LPLAT7 consumes unsaturated LPC formed by lysosomes. In mice, Lplat7 knockout increased the concentration of unsaturated lysophospholipids, reduced the abundance of 1-stearoyl-2-unsaturated species of phosphatidylcholine, phosphatidylethanolamine, and phosphatidylserine, and inhibited the regeneration of cellular membranes. It also triggered the accumulation of triglycerides, confirming earlier reports that unsaturated lysophospholipids induce lipid droplet formation. Thus, by re-acylating unsaturated 1-lysophospholipids, LPLAT7 shifts lipid metabolism from the biogenesis of lipid droplets to the biogenesis of membranes.
Keywords:
Lipidomics
lysophospholipid
phospholipase A
phospholipid/biosynthesis
phospholipid/metabolism
CL
cardiolipin
ER
endoplasmic reticulum
LPC
lysophosphatidylcholine
LPE
lysophosphatidylethanolamine
LPG
lysophosphatidylglycerol
LPLAT
lysophospholipid acyltransferase
LPS
lysophosphatidylserine
MLCL
monolyso-cardiolipin
PA
phosphatidic acid
PC
phosphatidylcholine
PE
phosphatidylethanolamine
PG
phosphatidylglycerol
PLA
phospholipase A
PS
phosphatidylserine
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