Lysophospholipid Acyltransferases Mediate Phosphatidylcholine Diversification to Achieve the Physical Properties Required In Vivo

• A model for acyl-chain diversification in phosphatidylcholine (PC) is proposed
• Lysophospholipid acyltransferases of different pathways regulate PC composition
• This model explains how PC composition is regulated in pulmonary surfactant
• Pulmonary surfactant PC dysregulation increases susceptibility to acute lung injury

SummaryThe acyl-chain composition of the major mammalian phospholipid phosphatidylcholine (PC) is distinct in various tissues. Although it was classically suggested that PC diversity is acquired through acyl-chain remodeling, the mechanisms and biological relevance of acyl-chain diversity remain unclear. Here, we show that differences in the substrate selectivity of lysophospholipid acyltransferases regulate tissue PC acyl-chain composition through contribution of both the de novo and remodeling pathways, depending on the fatty acid species. Unexpectedly, while dipalmitoyl-PC (DPPC) is enriched through the remodeling pathway, several polyunsaturated PC molecules accumulate during the de novo pathway. We confirmed this concept for DPPC in pulmonary surfactant and showed that the biophysical properties of this lipid are important to prevent the early onset of acute lung injury. We propose a model of harmonized processes for phospholipid diversification to satisfy in vivo requirements, with an example of its biological relevance.

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