Open AccessRegulation of copper homeostasis by Cuf1 associates with its subcellular localization in the pathogenic yeast Cryptococcus neoformans H99
Author(s) -
Jiang Nan,
Liu Xiaoguang,
Yang Jiao,
Li Zhongming,
Pan Jiao,
Zhu Xudong
Publication year - 2011
Publication title -
fems yeast research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.991
H-Index - 92
eISSN - 1567-1364
pISSN - 1567-1356
DOI - 10.1111/j.1567-1364.2011.00733.x
Subject(s) - copper , biology , subcellular localization , yeast , copper toxicity , biochemistry , saccharomyces cerevisiae , mutant , intracellular , copper deficiency , microbiology and biotechnology , cytoplasm , chemistry , gene , organic chemistry
Here, we present further characterization of cryptococcal CUF1 in copper homeostasis. We demonstrated that CUF1 was involved both in copper acquisition and in copper detoxification in response to copper variation. This was verified by direct measurement of the quantity of intracellular copper with flame atomic absorption spectrometry (FAAS) and molecular evidence. In copper‐limited growth, the mutant cuf1 Δ exhibited copper deficiency, growth defect on glycerol and sensitivity to hydrogen peroxide and methionine. A novel function of cryptococcal CUF1 is revealed in copper detoxification when copper is in excess. The mutant cuf1 Δ showed severe hypersensitivity to exogenous copper, while a high level of copper was accumulated shown by FAAS, suggesting that CUF1 may be required in copper export events. On cloning of cDNA, it was found that Cuf1 distinguishably harbors functional elements that are found in Ace1 and Mac1 of Saccharomyces cerevisiae . The regulation of copper homeostasis by Cuf1 is realized by its subcellular localization. Epifluorescence microscopy observed that, upon copper depletion, Cuf1 was localized exclusively to the nucleus as an activator for CTR4 transcription, while it was located to the cell periphery in the presence of exogenous copper. This work reveals a unique copper regulator and may provide insights into the copper metabolism in fungi.