Submitted on December 10, 2002
Revised on December 30, 2002
Accepted on January 2, 2003
New perspectives on the regulation of inter-membrane glycerophospholipid traffic
Dennis R. Voelker
Medicine Dept., National Jewish Medical and Research Center, Denver, CO 80206
Corresponding Author: voelkerd{at}njc.org
In eukaryotes, phosphatidylserine (PtdSer) can serve as a precursor of phosphatidylethanolamine (PtdEtn) and phosphatidylcholine (PtdCho). These three aminoglycerophospholipids typically constitute 70-80% of all membrane phospholipids in eukaryotic cells. PtdSer synthesis originates in the endoplasmic reticulum (ER) and a specialized subdomain named the mitochondria associated membrane (MAM). Nascent PtdSer is transported to the mitochondria in mammalian cells and yeast, and decarboxylated by Psd1p to form PtdEtn. A second decarboxylase, Psd2p is also found in yeast in the Golgi/vacuole. PtdEtn produced by Psd1p and Psd2p can be transported to the ER where it is methylated to form PtdCho. The organelle specific metabolism of the aminoglycerophospholipids is a powerful tool for following inter-organelle lipid traffic at the cellular, biochemical and genetic level. These analyses are now identifying new proteins involved in the regulation of aminoglycerophospholipid traffic among organelles. Genetic experiments demonstrate that transport of PtdSer between the MAM and mitochondria is regulated by protein ubiquitination. Reconstitution experiments reveal that ubiquitination affects lipid transport at the donor side of the reaction originating in the MAM and the acceptor side of the reaction in the mitochondria. Analysis of PtdSer transport to the locus of Psd2p now indicates that a membrane bound phosphatidylinositol transfer protein (PstB2p) is required on the acceptor membrane for efficient transport of PtdSer to the enzyme. In conjunction with PstB2p, the C2 domain of Psd2p is also required for PtdSer transport to the enzyme. Collectively, these recent findings indicate that novel multiprotein assemblies on both donor and acceptor membranes contribute to inter-organelle phospholipid transport.
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