Alonso-Monge Rebeca, Carvaihlo Sara, Nombela Cesar, Rial Eduardo, Pla Jesús
Departamento de Microbiología II, Facultad de Farmacia, Universidad Complutense de Madrid, Plaza de Ramón y Cajal s/n, E-28040 Madrid, Spain.
Departamento de Ciencias de Proteínas, Centro de Investigaciones Biológicas, CSIC, Ramiro de Maeztu 9, E-28040 Madrid, Spain.
Microbiology (Reading). 2009 Feb;155(Pt 2):413-423. doi: 10.1099/mic.0.023309-0.
Signal transduction pathways mediated by mitogen-activated protein kinases (MAPKs) play crucial roles in eukaryotic cells. In the pathogenic fungus Candida albicans the HOG MAPK pathway regulates the response to external stresses (osmotic and oxidative among others) and is involved in morphogenesis and virulence. We show here that the lack of the Hog1 MAPK increases the sensitivity of this fungus to inhibitors of the respiratory chain. hog1 mutants also show an enhanced basal respiratory rate compared to parental strains, and higher levels of intracellular reactive oxygen species despite an increased expression of detoxifying enzymes. We also demonstrate that although oxidative phosphorylation is essentially unaffected, hog1 mutants have an altered mitochondrial membrane potential. Data indicate that hog1-defective mutants are more dependent on mitochondrial ATP synthesis, probably due to an increased cellular ATP demand. Our results therefore link a MAPK pathway with respiratory metabolism in pathogenic fungi.
由丝裂原活化蛋白激酶（MAPK）介导的信号转导途径在真核细胞中发挥着关键作用。在致病性真菌白色念珠菌中，HOG MAPK途径调节对外部应激（如渗透压和氧化应激等）的反应，并参与形态发生和毒力。我们在此表明，Hog1 MAPK的缺失增加了这种真菌对呼吸链抑制剂的敏感性。与亲本菌株相比，hog1突变体还表现出增强的基础呼吸速率，尽管解毒酶的表达增加，但细胞内活性氧水平更高。我们还证明，尽管氧化磷酸化基本未受影响，但hog1突变体的线粒体膜电位发生了改变。数据表明，hog1缺陷型突变体更依赖线粒体ATP合成，这可能是由于细胞ATP需求增加所致。因此，我们的结果将一条MAPK途径与致病性真菌的呼吸代谢联系了起来。
