LPLAT10/LPEAT2 produces atypical phospholipids with an unsaturated FA at the sn-1 position

Major membrane phospholipids (PLs) contain saturated FAs, such as palmitic acid (C16:0) and stearic acid (C18:0), at the sn-1 position. Although atypical PLs containing unsaturated FAs at the sn-1 position exist as minor components, the biosynthetic pathway responsible for their production has remained elusive. Here, we report that LPLAT10 (also known as LPEAT2 or LPCAT4) is a lysophospholipid acyltransferase responsible for generating PLs with an unsaturated FA at the sn-1 position. In vitro, LPLAT10 incorporated both saturated and unsaturated FAs into lysophosphatidylcholine, lysophosphatidylethanolamine, and lysophosphatidylserine, selectively at the sn-1 position. LPLAT10 appeared to have a relatively higher affinity for unsaturated FA-CoAs. Consistently, only PLs with unsaturated FAs such as oleic acid (C18:1), linoleic acid (C18:2), arachidonic acid (C20:4), and DHA (C22:6) at the sn-1 position decreased in the brain from Lplat10-deficient mice. Despite their low abundance, these atypical PLs may have specific roles, given that LPLAT10 is highly expressed in neurons and its encoding genes are highly conserved among vertebrates above fish.