Protective roles of mitochondrial manganese-containing superoxide dismutase against various stresses in Candida albicans.
Candida albicans contains copper- and zinc-containing superoxide dismutase but also two manganese-containing superoxide dismutases (MnSODs), one in the cytosol and the other in the mitochondria. Among these, the SOD2 gene encoding mitochondrial MnSOD was disrupted and overexpressed to investigate its roles in C. albicans. The null mutant lacking mitochondrial MnSOD was more sensitive than wild-type cells to various stresses, such as redox-cycling agents, heating, ethanol, high concentration of sodium or potassium and 99.9% O2. Interestingly, the sod2/sod2 mutant was rather more resistant to lithium and diamide than the wild-type, whereas overexpression of SOD2 increased susceptibility of C. albicans to these compounds. The inverse effect of mitochondrial MnSOD on lithium toxicity was relieved when the sod2/sod2 and SOD2-overexpressing cells were grown on the synthetic dextrose medium containing sulphur compounds such as methionine, cysteine, glutathione or sulphite, indicating that mitochondrial MnSOD may affect lithium toxicity through sulphur metabolism. Moreover, disruption or overexpression of SOD2 increased or decreased glutathione reductase activity and cyanide-resistant respiration by alternative oxidase, respectively. Taken together, these findings suggest that mitochondrial MnSOD is important for stress responses, lithium toxicity and cyanide-resistant respiration of C. albicans.
Hwang
Cheol-Sang
CS
Laboratory of Biophysics, School of Biological Sciences, Seoul National University, Seoul 151-742, Republic of Korea.
Baek
Yong-Un
YU
Yim
Hyung-Soon
HS
Kang
Sa-Ouk
SO
D002176:Candida albicans / Q000187:drug effects / Q000201:enzymology* / Q000235:genetics; D019069:Cell Respiration / Q000187:drug effects; D003486:Cyanides / Q000633:toxicity; D003958:Diamide / Q000633:toxicity; D015971:Gene Expression Regulation, Enzymologic; D015966:Gene Expression Regulation, Fungal; D008094:Lithium / Q000633:toxicity; D008928:Mitochondria / Q000201:enzymology* / Q000235:genetics; D024101:Mitochondrial Proteins; D016254:Mutagenesis, Insertional; D018384:Oxidative Stress / Q000502:physiology; D010088:Oxidoreductases / Q000096:biosynthesis / Q000378:metabolism; D010269:Paraquat / Q000633:toxicity; D010940:Plant Proteins; D013482:Superoxide Dismutase / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D024483:Vitamin K 3 / Q000633:toxicity; D000099188:Alternative Oxidase
D003486:Cyanides; D003958:Diamide; D008094:Lithium; D024101:Mitochondrial Proteins; D010088:Oxidoreductases; D010269:Paraquat; D010940:Plant Proteins; D013482:Superoxide Dismutase; D024483:Vitamin K 3; D000099188:Alternative Oxidase