The Rbf1, Hfl1 and Dbp4 of Candida albicans regulate common as well as transcription factor-specific mitochondrial and other cell activities.
BACKGROUND
Our interest in Candida albicans mitochondria began with the identification of GOA1. We demonstrated its role in cell energy production, cross-talk among mitochondria and peroxisomes, non-glucose energy metabolism, maintenance of stationary phase growth, and prevention of premature apoptosis. Its absence results in avirulence. However, what regulated transcription of GOA1 was unknown.


RESULTS
To identify transcriptional regulators (TRs) of GOA1, we screened a C. albicans TF knockout library (TRKO) and identified Rbf1p, Hfl1p, and Dpb4p as positive TRs of GOA1. The phenotypes of each mutant (reduced respiration, inability to grow on glycerol, reduced ETC CI and CIV activities) are reasonable evidence for their required roles especially in mitochondrial functions. While the integration of mitochondria with cell metabolic activities is presumed to occur, there is minimal information on this subject at the genome level. Therefore, microarray analysis was used to provide this information for each TR mutant. Transcriptional profiles of Rbf1p and Hfl1p are more similar than that of Dpn4p. Our data demonstrate common and also gene-specific regulatory functions for each TR. We establish their roles in carbon metabolism, stress adaptation, cell wall synthesis, transporter efflux, peroxisomal metabolism, phospholipid synthesis, rRNA processing, and nuclear/mtDNA replication.


CONCLUSIONS
The TRs regulate a number of common genes but each also regulates specific gene transcription. These data for the first time create a genome roadmap that can be used to integrate mitochondria with other cell processes. Of interest, the TRs are fungal-specific, warranting consideration as antifungal drug targets.
Kasra
K
Khamooshi
Patricia
P
Sikorski
Nuo
N
Sun
Richard
R
Calderone
Department of Microbiology & Immunology, Georgetown University Medical Center, Washington DC 20057, USA. dl33@georgetown.edu.
Dongmei
D
Li
D000935:Antifungal Agents / Q000494:pharmacology; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism; D002176:Candida albicans / Q000235:genetics* / Q000378:metabolism; D002244:Carbon / Q000378:metabolism; D019069:Cell Respiration / Q000235:genetics; D002473:Cell Wall / Q000187:drug effects; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000235:genetics / Q000378:metabolism; D055786:Gene Knockout Techniques; D015723:Gene Library; D015227:Lipid Peroxidation / Q000235:genetics; D008928:Mitochondria / Q000378:metabolism*; D009687:Nuclear Proteins / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism; D010641:Phenotype; D014157:Transcription Factors / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism; D059467:Transcriptome / Q000187:drug effects
D000935:Antifungal Agents; D029742:Caenorhabditis elegans Proteins; D004268:DNA-Binding Proteins; D005656:Fungal Proteins; C516620:GOA-1 protein, C elegans; D009687:Nuclear Proteins; C104796:RBF1 protein, Candida albicans; D014157:Transcription Factors; D002244:Carbon; D019206:GTP-Binding Protein alpha Subunits, Gi-Go