title: Mitochondrial two-component signaling systems in Candida albicans.
abstract: Two-component signal transduction pathways are one of the primary means by which microorganisms respond to environmental signals. These signaling cascades originated in prokaryotes and were inherited by eukaryotes via endosymbiotic lateral gene transfer from ancestral cyanobacteria. We report here that the nuclear genome of the pathogenic fungus Candida albicans contains elements of a two-component signaling pathway that seem to be targeted to the mitochondria. The C. albicans two-component response regulator protein Srr1 (stress response regulator 1) contains a mitochondrial targeting sequence at the N terminus, and fluorescence microscopy reveals mitochondrial localization of green fluorescent protein-tagged Srr1. Moreover, phylogenetic analysis indicates that C. albicans Srr1 is more closely related to histidine kinases and response regulators found in marine bacteria than are other two-component proteins present in the fungi. These data suggest conservation of this protein during the evolutionary transition from endosymbiont to a subcellular organelle. We used microarray analysis to determine whether the phenotypes observed with a srr1Δ/Δ mutant could be correlated with gene transcriptional changes. The expression of mitochondrial genes was altered in the srr1Δ/Δ null mutant in comparison to their expression in the wild type. Furthermore, apoptosis increased significantly in the srr1Δ/Δ mutant strain compared to the level of apoptosis in the wild type, suggesting the activation of a mitochondrion-dependent apoptotic cell death pathway in the srr1Δ/Δ mutant. Collectively, this study shows for the first time that a lower eukaryote like C. albicans possesses a two-component response regulator protein that has survived in mitochondria and regulates a subset of genes whose functions are associated with the oxidative stress response and programmed cell death (apoptosis).
authors.affiliation: Public Health Research Institute, University of Medicine and Dentistry of New Jersey, Newark, New Jersey, USA.
authors.forename: John
authors.initials: J
authors.lastname: Mavrianos
authors.forename: Elizabeth L
authors.initials: EL
authors.lastname: Berkow
authors.forename: Chirayu
authors.initials: C
authors.lastname: Desai
authors.forename: Alok
authors.initials: A
authors.lastname: Pandey
authors.forename: Mona
authors.initials: M
authors.lastname: Batish
authors.forename: Marissa J
authors.initials: MJ
authors.lastname: Rabadi
authors.forename: Katherine S
authors.initials: KS
authors.lastname: Barker
authors.forename: Debkumar
authors.initials: D
authors.lastname: Pain
authors.forename: P David
authors.initials: PD
authors.lastname: Rogers
authors.forename: Eliseo A
authors.initials: EA
authors.lastname: Eugenin
authors.forename: Neeraj
authors.initials: N
authors.lastname: Chauhan
mesh_terms: D000595:Amino Acid Sequence; D017209:Apoptosis; D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism; D005075:Biological Evolution; D002176:Candida albicans / Q000235:genetics* / Q000378:metabolism / Q000648:ultrastructure; D005656:Fungal Proteins / Q000235:genetics* / Q000378:metabolism; D017353:Gene Deletion; D015966:Gene Expression Regulation, Fungal; D006360:Heat-Shock Proteins / Q000172:deficiency / Q000235:genetics*; D000071677:Histidine Kinase; D008928:Mitochondria / Q000378:metabolism* / Q000648:ultrastructure; D008969:Molecular Sequence Data; D010802:Phylogeny; D011494:Protein Kinases / Q000172:deficiency / Q000235:genetics*; D021381:Protein Transport; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction
chemical_list: D001426:Bacterial Proteins; D005656:Fungal Proteins; D006360:Heat-Shock Proteins; D011993:Recombinant Fusion Proteins; D011494:Protein Kinases; D000071677:Histidine Kinase