Subcellular localization and lysophospholipase/transacylation activities of human group IVC phospholipase A2 (cPLA2 gamma)

cPLA2 gamma was identified as an ortholog of cPLA2 alpha, which is a key enzyme in eicosanoid production. cPLA2 gamma was reported to be located in endoplasmic reticulum (ER) and mitochondria and to have lysophospholipase activity beside phospholipase A2 (PLA2) activity. However, subcellular localization, mechanism of membrane binding, regulation and physiological function have not been fully established. In the present study, we examined the subcellular localization and enzymatic properties of cPLA2 gamma with C-terminal FLAG-tag. We found that cPLA2 gamma was located not only in ER but also mitochondria even in the absence of the prenylation. Purified recombinant cPLA2 gamma catalyzed an acyltransferase reaction from one molecule of lysophosphatidylcholine (LPC) to another, forming phosphatidylcholine (PC). LPC or lysophosphatidylethanolamine acted as acyl donor and acceptor, but lysophosphatidylserine, lysophosphatidylinositol and lysophosphatidic acid (LPA) did not. PC and phosphatidylethanolamine (PE) also acted as weak acyl donors. Reaction conditions changed the balance of lysophospholipase and transacylation activities, with addition of LPA/PA, pH>8, and elevated temperature markedly increasing transacylation activity; this suggests that lysophospholipase/transacylation activities of cPLA2 gamma may be regulated by various factors. As lysophospholipids are known to accumulate in ischemia heart and to induce arryhthmia, the cPLA2 gamma that is abundant in heart may have a protective role through clearance of lysophospholipids by its transacylation activity. (C) 2009 Elsevier B.V. All rights reserved.