Functional diversity of complex I subunits in Candida albicans mitochondria
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  • 作者:Dongmei Li ; Xiaodong She ; Richard Calderone
  • 关键词:Accessory subunits ; Mitochondria ; Cristae formation ; Candida albicans
  • 刊名:Current Genetics
  • 出版年:2016
  • 出版时间:February 2016
  • 年:2016
  • 卷:62
  • 期:1
  • 页码:87-95
  • 全文大小:483 KB
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  • 作者单位:Dongmei Li (1)
    Xiaodong She (2)
    Richard Calderone (1)

    1. Department of Microbiology and Immunology, Georgetown University Medical Center, Washington, DC, 20057, USA
    2. Jiangsu Key Laboratory of Molecular Biology for Skin Disease and STIs, Institute of Dermatology, Chinese Academy of Medical Sciences (CAMS), Nanjing, 210029, China
  • 刊物类别:Biomedical and Life Sciences
  • 刊物主题:Life Sciences
    Microbial Genetics and Genomics
    Microbiology
    Biochemistry
    Cell Biology
    Plant Sciences
    Proteomics
  • 出版者:Springer Berlin / Heidelberg
  • ISSN:1432-0983
文摘
Our interest in the mitochondria of Candida albicans has progressed to the identification of several proteins that are critical to complex I (CI) activity. We speculated that there should be major functional differences at the protein level between mammalian and fungal mitochondria CI. In our pursuit of this idea, we were helped by published data of CI subunit proteins from a broad diversity of species that included two subunit proteins that are not found in mammals. These subunit proteins have been designated as Nuo1p and Nuo2p (NADH-ubiquinone oxidoreductases). Since functional assignments of both C. albicans proteins were unknown, other than having a putative NADH-oxidoreductase activity, we constructed knock-out strains that could be compared to parental cells. The relevance of our research relates to the critical roles of both proteins in cell biology and pathogenesis and their absence in mammals. These features suggest they may be exploited in antifungal drug discovery. Initially, we characterized Goa1p that apparently regulates CI activity but is not a CI subunit protein. We have used the goa1∆ for comparisons to Nuo1p and Nuo2p. We have demonstrated the critical role of these proteins in maintaining CI activities, virulence, and prolonging life span. More recently, transcriptional profiling of the three mutants and an ndh51∆ (protein is a highly conserved CI subunit) has revealed that there are overlapping yet also different functional assignments that suggest subunit specificity. The differences and similarities of each are described below along with our hypotheses to explain these data. Our conclusion and perspective is that the C. albicans CI subunit proteins are highly conserved except for two that define non-mammalian functions. Keywords Accessory subunits Mitochondria Cristae formation Candida albicans

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