Rhodotorula glutinis IFO1125 acquired increased aluminum (Al) resistance from 50 mu M to more than 5 mM by repetitive culturing with stepwise increases in Al concentration at pH 4.0. In our previous study we performed differential display to find that three genes (RgFET3, RgGET3, and RgCMK) encoding proteins homologous to Saccharomyces cerevisiae FET3p, GET3p, and CMK1p and CMK2p, respectively, were up-regulated in the Al-resistant cells. In this study we cloned these genes and found they were indeed up-regulated in Al-resistant strains. The cloned genes were introduced into S. cerevisiae and corresponding mutants to test their relevance to Al resistance. The introduction of RgFET3 and RgGET3 conferred Al resistance to the host, but that of RgCMK did not. Green fluorescent protein (GFP)-tagged RgFet3p was localized at the cell periphery in the host. GFP-tagged RgGet3p formed more punctate bodies in the host under Al stress than in the absence of Al. Different growth responses to Fe (III), Cu (II), Ca ions, and cyclosporin A in the wild type and resistant cells of R. glutinis suggested the involvement and possible links of the three genes in Al resistance. (C) 2009, The Society for Biotechnology, Japan. All rights reserved.