机构：[1]Department of Microbiology & Immunology, Georgetown University Medical Center, Washington, DC 20057, USA[2]Sport Science Research Center, Shandong Sport University, Jinan 250102, China[3]Department of Dermatology, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650031, China内科科室皮肤科昆明医科大学附属第一医院[4]Institute of Microbiology and Parasitology, Medical Faculty University Sts Cyril and Methodius, 50 Divizija. No. 6, 1000 Skopje, Macedonia
We have previously established that mitochondrial Complex I (CI) mutants of Candida albicans display reduced oxygen consumption, decreased ATP production, and increased reactive oxidant species (ROS) during cell growth. Using the Seahorse XF96 analyzer, the energetic phenotypes of Electron Transport Chain (ETC) complex mutants are further characterized in the current study. The underlying regulation of energetic changes in these mutants is determined in glucose and non-glucose conditions when compared to wild type (WT) cells. In parental cells, the rate of oxygen consumption remains constant for 2.5 h following the addition of glucose, oligomycin, and 2-DG, but glycolysis is highly active upon the addition of glucose. In comparison, over the same time period, electron transport complex mutants (CI, CIII and CIV) have heightened activities in both oxygen consumption and glycolysis upon glucose uptake. We refer to the response in these mutants as an "explosive respiration," which we believe is caused by low energy levels and increased production of reactive oxygen species (ROS). Accompanying this phenotype in mutants is a hyperphosphorylation of Snf1p which in Saccharomyces cerevisiae serves as an energetic stress response protein kinase for maintaining energy homeostasis. Compared to wild type cells, a 2.9- to 4.4-fold hyperphosphorylation of Snf1p is observed in all ETC mutants in the presence of glucose. However, the explosive respiration and hyperphosphorylation of Snf1 can be partially reduced by the replacement of glucose with either glycerol or oleic acid in a mutant-specific manner. Furthermore, Inhibitors of glutathione synthesis (BSO) or anti-oxidants (mito-TEMPO) likewise confirmed an increase of Sfn1 phosphorylation in WT or mutant due to increased levels of ROS. Our data establish the role of the C. albicans Snf1 as a surveyor of cell energy and ROS levels. We interpret the "explosive respiration" as a failed attempt by ETC mutants to restore energy and ROS homeostasis via Snf1 activation. An inherently high OCR baseline in WT C. albicans with a background level of Snf1 activation is a prerequisite for success in quickly fermenting glucose.
基金：
Natural Science Foundation of Shandong Province, ChinaNatural Science Foundation of Shandong Province [ZR2017LC013]; Higher Education Priority Academic Talent Development Program of Shandong Province; Applied Basic Science of Yunnan, China [2014FB030]; Biomedical Graduate Research Organization
第一作者机构：[1]Department of Microbiology & Immunology, Georgetown University Medical Center, Washington, DC 20057, USA[2]Sport Science Research Center, Shandong Sport University, Jinan 250102, China
共同第一作者：
通讯作者：
通讯机构：[*1]Department of Microbiology & Immunology, Georgetown University Medical Center, 3900 Reservoir Rd, NW, Washington, DC 20057, USA
推荐引用方式(GB/T 7714)：
Zhang Pengyi,Li Hongbin,Cheng Jie,et al.Respiratory stress in mitochondrial electron transport chain complex mutants of Candida albicans activates Snf1 kinase response[J].FUNGAL GENETICS AND BIOLOGY.2018,111:73-84.doi:10.1016/j.fgb.2017.11.002.
APA：
Zhang, Pengyi,Li, Hongbin,Cheng, Jie,Sun, April Y.,Wang, Liqing...&Li, Dongmei.(2018).Respiratory stress in mitochondrial electron transport chain complex mutants of Candida albicans activates Snf1 kinase response.FUNGAL GENETICS AND BIOLOGY,111,
MLA：
Zhang, Pengyi,et al."Respiratory stress in mitochondrial electron transport chain complex mutants of Candida albicans activates Snf1 kinase response".FUNGAL GENETICS AND BIOLOGY 111.(2018):73-84
