The lipid-translocating exporter family and membrane phospholipid homeostasis in yeast.
The fungal lipid-translocating exporter family consists of conserved membrane proteins, with six or seven transmembrane spans. Phylogenetic trees and conserved gene order relationships show that the common ancestor of five closely related hemiascomycetous yeast species contained the RSB1 and PUG1 paralogous genes. In Saccharomyces cerevisiae, Rsb1 functions as a transporter or translocase of sphingoid bases, whereas Pug1 facilitates the inducible transport of protoporphyrin IX and hemin. The budding yeast contains two other paralogs, Ylr046p, of unknown function, and Rta1p, overexpression of which confers resistance to an ergosterol biosynthesis inhibitor. Large-scale mRNA expression profiling has shown that transcription of PUG1, RTA1 and YLR046 is induced under hypoxic conditions. Ergosterol biosynthesis is impaired under low-oxygen conditions as a consequence of the decreased synthesis of heme and heme-containing proteins. These genes may encode transporters or sensors that facilitate the excretion of excessive or aberrant biosynthetic intermediates, either directly or indirectly. The expression of RSB1 and RTA1 is under the control of pleiotropic drug resistance transcription factors, suggesting that the encoded proteins may have additional roles in cell resistance to xenobiotics. This review summarizes current knowledge concerning the lipid-translocating exporter family and its potential functions, focusing on multidrug resistance and membrane phospholipid homeostasis.
Unité de biochimie physiologique, Institut des sciences de la vie, Université catholique de Louvain, Croix du Sud 5-15, Louvain-la-Neuve, Belgium.
Myriam
M
Manente
Michel
M
Ghislain
D002462:Cell Membrane / Q000737:chemistry* / Q000378:metabolism*; D026141:Drug Resistance, Multiple, Fungal; D005656:Fungal Proteins / Q000378:metabolism*; D015966:Gene Expression Regulation, Fungal; D049294:Phospholipid Transfer Proteins / Q000378:metabolism*; D010743:Phospholipids / Q000032:analysis*; D012441:Saccharomyces cerevisiae / Q000502:physiology*
D005656:Fungal Proteins; D049294:Phospholipid Transfer Proteins; D010743:Phospholipids