ABC transporters in lipid transport

Biochim Biophys Acta. 2000 Jun 26;1486(1):128-44. doi: 10.1016/s1388-1981(00)00053-6.

Abstract

Since it was found that the P-glycoproteins encoded by the MDR3 (MDR2) gene in humans and the Mdr2 gene in mice are primarily phosphatidylcholine translocators, there has been increasing interest in the possibility that other ATP binding cassette (ABC) transporters are involved in lipid transport. The evidence reviewed here shows that the MDR1 P-glycoprotein and the multidrug resistance (-associated) transporter 1 (MRP1) are able to transport lipid analogues, but probably not major natural membrane lipids. Both transporters can transport a wide range of hydrophobic drugs and may see lipid analogues as just another drug. The MDR3 gene probably arose in evolution from a drug-transporting P-glycoprotein gene. Recent work has shown that the phosphatidylcholine translocator has retained significant drug transport activity and that this transport is inhibited by inhibitors of drug-transporting P-glycoproteins. Whether the phosphatidylcholine translocator also functions as a transporter of some drugs in vivo remains to be seen. Three other ABC transporters were recently shown to be involved in lipid transport: ABCR, also called Rim protein, was shown to be defective in Stargardt's macular dystrophy; this protein probably transports a complex of retinaldehyde and phosphatidylethanolamine in the retina of the eye. ABC1 was shown to be essential for the exit of cholesterol from cells and is probably a cholesterol transporter. A third example, the ABC transporter involved in the import of long-chain fatty acids into peroxisomes, is discussed in the chapter by Hettema and Tabak in this volume.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • ATP Binding Cassette Transporter 1
  • ATP Binding Cassette Transporter, Subfamily B / genetics
  • ATP Binding Cassette Transporter, Subfamily B / metabolism
  • ATP-Binding Cassette Transporters / genetics
  • ATP-Binding Cassette Transporters / metabolism*
  • Animals
  • Bacterial Proteins / metabolism
  • Bile / metabolism
  • Biological Transport
  • Carrier Proteins / metabolism
  • Drug Resistance, Multiple
  • Glycoproteins / metabolism
  • Humans
  • Lipid Metabolism*
  • Liver / metabolism
  • Membrane Lipids / metabolism
  • Membrane Proteins / metabolism
  • Multidrug Resistance-Associated Proteins
  • Phosphatidylcholines / metabolism
  • Phospholipid Transfer Proteins*
  • Substrate Specificity
  • Transfection

Substances

  • ABCA1 protein, human
  • ABCA4 protein, human
  • ATP Binding Cassette Transporter 1
  • ATP Binding Cassette Transporter, Subfamily B
  • ATP-Binding Cassette Transporters
  • Bacterial Proteins
  • Carrier Proteins
  • Glycoproteins
  • LmrA protein, Lactococcus lactis
  • Membrane Lipids
  • Membrane Proteins
  • Multidrug Resistance-Associated Proteins
  • Phosphatidylcholines
  • Phospholipid Transfer Proteins
  • multidrug resistance protein 3