Mitochondrial two-component signaling systems in Candida albicans

John Mavrianos, Elizabeth L. Berkow, Chirayu Desai, Alok Pandey, Mona Batish, Marissa J. Rabadi, Katherine S. Barker, Debkumar Pain, P. David Rogers, Eliseo Eugenin, Neeraj Chauhan

Research output: Contribution to journalArticle

13 Citations (Scopus)

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).

Original languageEnglish (US)
Pages (from-to)913-922
Number of pages10
JournalEukaryotic Cell
Volume12
Issue number6
DOIs
StatePublished - Jun 1 2013
Externally publishedYes

Fingerprint

Candida albicans
Mitochondria
Apoptosis
Eukaryota
Fungi
Cell Death
Horizontal Gene Transfer
Proteins
Mitochondrial Genes
Cyanobacteria
Microarray Analysis
Heat-Shock Proteins
Green Fluorescent Proteins
Fluorescence Microscopy
Organelles
Genes
Signal Transduction
Oxidative Stress
Genome
Bacteria

ASJC Scopus subject areas

  • Microbiology
  • Molecular Biology

Cite this

Mavrianos, J., Berkow, E. L., Desai, C., Pandey, A., Batish, M., Rabadi, M. J., ... Chauhan, N. (2013). Mitochondrial two-component signaling systems in Candida albicans. Eukaryotic Cell, 12(6), 913-922. https://doi.org/10.1128/EC.00048-13

Mitochondrial two-component signaling systems in Candida albicans. / Mavrianos, John; Berkow, Elizabeth L.; Desai, Chirayu; Pandey, Alok; Batish, Mona; Rabadi, Marissa J.; Barker, Katherine S.; Pain, Debkumar; Rogers, P. David; Eugenin, Eliseo; Chauhan, Neeraj.

In: Eukaryotic Cell, Vol. 12, No. 6, 01.06.2013, p. 913-922.

Research output: Contribution to journalArticle

Mavrianos, J, Berkow, EL, Desai, C, Pandey, A, Batish, M, Rabadi, MJ, Barker, KS, Pain, D, Rogers, PD, Eugenin, E & Chauhan, N 2013, 'Mitochondrial two-component signaling systems in Candida albicans', Eukaryotic Cell, vol. 12, no. 6, pp. 913-922. https://doi.org/10.1128/EC.00048-13
Mavrianos J, Berkow EL, Desai C, Pandey A, Batish M, Rabadi MJ et al. Mitochondrial two-component signaling systems in Candida albicans. Eukaryotic Cell. 2013 Jun 1;12(6):913-922. https://doi.org/10.1128/EC.00048-13
Mavrianos, John ; Berkow, Elizabeth L. ; Desai, Chirayu ; Pandey, Alok ; Batish, Mona ; Rabadi, Marissa J. ; Barker, Katherine S. ; Pain, Debkumar ; Rogers, P. David ; Eugenin, Eliseo ; Chauhan, Neeraj. / Mitochondrial two-component signaling systems in Candida albicans. In: Eukaryotic Cell. 2013 ; Vol. 12, No. 6. pp. 913-922.
@article{b543d141930447d395c285096bcf3a16,
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).",
author = "John Mavrianos and Berkow, {Elizabeth L.} and Chirayu Desai and Alok Pandey and Mona Batish and Rabadi, {Marissa J.} and Barker, {Katherine S.} and Debkumar Pain and Rogers, {P. David} and Eliseo Eugenin and Neeraj Chauhan",
year = "2013",
month = "6",
day = "1",
doi = "10.1128/EC.00048-13",
language = "English (US)",
volume = "12",
pages = "913--922",
journal = "Eukaryotic Cell",
issn = "1535-9778",
publisher = "American Society for Microbiology",
number = "6",

}

TY - JOUR

T1 - Mitochondrial two-component signaling systems in Candida albicans

AU - Mavrianos, John

AU - Berkow, Elizabeth L.

AU - Desai, Chirayu

AU - Pandey, Alok

AU - Batish, Mona

AU - Rabadi, Marissa J.

AU - Barker, Katherine S.

AU - Pain, Debkumar

AU - Rogers, P. David

AU - Eugenin, Eliseo

AU - Chauhan, Neeraj

PY - 2013/6/1

Y1 - 2013/6/1

N2 - 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).

AB - 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).

UR - http://www.scopus.com/inward/record.url?scp=84878407525&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84878407525&partnerID=8YFLogxK

U2 - 10.1128/EC.00048-13

DO - 10.1128/EC.00048-13

M3 - Article

VL - 12

SP - 913

EP - 922

JO - Eukaryotic Cell

JF - Eukaryotic Cell

SN - 1535-9778

IS - 6

ER -