The development of MDR (multidrug resistance) in yeast is due to a number of mechanisms. The most documented mechanism is enhanced extrusion of drugs mediated by efflux pump proteins belonging to either the ABC (ATP-binding cassette) superfamily or MFS (major facilitator superfamily). These drug-efflux pump proteins are localized on the plasma membrane, and the milieu therein affects their proper functioning. Several recent studies demonstrate that fluctuations in membrane lipid composition affect the localization and proper functioning of the MDR efflux pump proteins. Interestingly, the efflux pumps of the ABC superfamily are particularly susceptible to imbalances in membrane-raft lipid constituents. This review focuses on the importance of the membrane environment in functioning of the drug-efflux pumps and explores a correlation between MDR and membrane lipid homoeostasis.
- lipid raft
- multidrug resistance (MDR)
Abbreviations: ABC, ATP-binding cassette; Ca, Candida albicans; FLR/FLU, fluconazole resistance; HSP12, heat-shock protein 12; IPC, inositol phosphoceramide; IPT, inositol phosphotransferase; LCB, long-chain base; LCBP, LCB phosphate; M(IP)2C, mannosyl bi-inositol diphosphoceramide; MDR, multidrug resistance; MFS, major facilitator superfamily; MIPC, mannosyl IPC; NBD, nucleotide-binding domain; NDT, non-dityrosine; PDR, pleiotropic drug resistance; PDRE, pleiotropic drug-response element; Pgp, P-glycoprotein; RSB, resistance to sphingoid base; RTA, resistance to 7-aminocholesterol; SNQ, sensitivity to 4-nitroquinoline-N-oxide; Tac, transcription activator of Cdr genes; TF, transcription factor; TMD, transmembrane domain; TMS, transmembrane-spanning segment; Upc, uptake control; YAP1, yeast activator protein 1; YOR, yeast oligomycin resistance; YRR, yeast reveromycin resistance
- © The Authors Journal compilation © 2008 Biochemical Society