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Journal of Lipid Research, Vol. 44, 441-449, March 2003
Copyright © 2003 by Lipid Research, Inc.
Thematic Review |
New perspectives on the regulation of intermembrane glycerophospholipid traffic
Program in Cell Biology, Department of Medicine, National Jewish Medical and Research Center, 1400 Jackson St., Denver, CO 80206
1 To whom correspondence should be addressed. e-mail: voelkerd{at}njc.org
In eukaryotes, phosphatidylserine (PtdSer) can serve as a precursor of phosphatidylethanolamine (PtdEtn) and phosphatidylcholine (PtdCho), which are the major cellular phospholipids. PtdSer synthesis originates in the endoplasmic reticulum (ER) and its subdomain named the mitochondria-associated membrane (MAM). PtdSer is transported to the mitochondria in mammalian cells and yeast, and decarboxylated by PtdSer decarboxylase 1 (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. Organelle-specific metabolism of the aminoglycerophospholipids is a powerful tool for experimentally following lipid traffic that is now enabling identification of new proteins involved in the regulation of this process. Genetic and biochemical experiments demonstrate that transport of PtdSer between the MAM and mitochondria is regulated by protein ubiquitination, which affects events at both membranes. Similar analyses of PtdSer transport to the locus of Psd2p now indicate that a membrane-bound phosphatidylinositol transfer protein and the C2 domain of Psd2p are both required on the acceptor membrane for efficient transport of PtdSer.
Collectively, these recent findings indicate that novel multiprotein assemblies on both donor and acceptor membranes participate in interorganelle phospholipid transport.
Abbreviations: ER, endoplasmic reticulum; MAM, mitochondria-associated membrane; PAM, plasma membrane-associated membrane; PtdCho, phosphatidylcholine; PtdEtn, phosphatidylethanolamine; PtdGro, phosphatidylglycerol; Ptd2Gro, cardiolipin; PtdIns, phosphatidylinositol; PtdOH, phosphatidic acid; PtdSer, phosphatidylserine
Supplementary key words membrane biogenesis • zones of apposition • transport complexes • aminoglycerophospholipids
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