GEF1 Is a Novel Factor Regulating Nickel Ion Metabolism in Saccharomyces cerevisiae

Nickel is a trace element essential for human life. Currently, studies on the metabolism and function of nickel ions mainly focus on prokaryotes, while the role of nickel ions in eukaryotes is still being explored. In this study, we found for the first time that GEF1 which encodes Gef1p, a chloride transport protein located in the Golgi membrane, is involved in nickel ion metabolism in yeast. The GEF1 knockout strain (gef1∆) showed strong resistance to excess nickel ions, and the content of nickel ions in gef1∆ cells was significantly elevated. The results of transcriptomics analysis showed significant upregulation of MMT2 and CUP1 in gef1∆ cells supplemented with nickel. Both MMT2 and CUP1 overexpressed in the gef1∆ strain showed a growth advantage on nickel media. Nickel ion content in the mitochondria of cells overexpressing MMT2 was significantly elevated, and the levels of reactive oxygen species were significantly decreased in strains overexpressing either the MMT2 or CUP1 genes. This study reveals that the GEF1 gene plays an important role in nickel homeostasis, and that upregulation of MMT2 and CUP1 is critical for gef1∆ strains to counteract ROS formation and growth defect by nickel ions.