Mitochondrial acyltransferases and glycerophospholipid metabolism

Our understanding of the synthesis and remodeling of mitochondrial phospholipids remains incomplete. Two isoforms of glycerol-3-phosphate acyltransferase (GPAT1 and 2) and two isoforms of acylglycerol-3-phosphate acyltransferase (AGPAT4 and 5) are located on the outer mitochondrial membrane, suggesting that both lysophosphatidic acid and phosphatidic acid are synthesized in situ for de novo glycerolipid biosynthesis. However, it is believed that the phosphatidic acid substrate for cardiolipin and phosphatidylethanolamine biosynthesis is produced at the endoplasmic reticulum whereas the phosphatidic acid synthesized in the mitochondria must be transferred to the endoplasmic reticulum before it undergoes additional steps to form the mature phospholipids that are trafficked back to the mitochondria. It is unclear whether mitochondrial phospholipids are remodeled by mitochondrial acyltransferases or whether lysophospholipids must return to the endoplasmic reticulum or to the mitochondrial associated membrane for reesterification. In this review we will focus on the few glycerolipid acyltransferases that are known to be mitochondrial. This article is part of a Special Issue entitled: Lipids of Mitochondria edited by Guenther Daum.