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Series GSE25891 Query DataSets for GSE25891
Status Public on Dec 10, 2010
Title Cell wall integrity is linked to mitochondria and phospholipid homeostasis in Candida albicans through the activity of the post-transcriptional regulator Ccr4-Pop2
Organism Candida albicans
Experiment type Expression profiling by array
Summary The cell wall is essential for viability of fungi and is an effective drug target in pathogens such as Candida albicans. The contribution of posttranscriptional gene regulators to cell wall integrity in C. albicans is unknown. We show that the C. albicans Ccr4-Pop2 mRNA deadenylase, a regulator of mRNA stability and translation, is required for cell wall integrity. The ccr4/pop2 mutants display reduced wall β-glucans and sensitivity to the echinocandin caspofungin. Moreover, the deadenylase mutants are compromised for filamentation and virulence. We demonstrate that defective cell walls in the ccr4/pop2 mutants are linked to dysfunctional mitochondria and phospholipid imbalance. To further understand mitochondrial function in cell wall integrity, we screened a Saccharomyces cerevisiae collection of mitochondrial mutants. We identify several mitochondrial proteins required for caspofungin tolerance and find a connection between mitochondrial phospholipid homeostasis and caspofungin sensitivity. We focus on the mitochondrial outer membrane SAM complex subunit Sam37, demonstrating it is required for both trafficking of phospholipids between the ER and mitochondria and cell wall integrity. Moreover, in C. albicans also Sam37 is essential for caspofungin tolerance. Our study provides the basis for an integrative view of mitochondrial function in fungal cell wall biogenesis and resistance to echinocandin antifungal drugs.
Overall design Two-color experimental design comparing cells with a double-knockout of the CCR4 genes to cells with a reintegrated CCR4 gene.
Contributor(s) Dagley MJ, Beaurepaire C, Nantel A, Traven A
Citation(s) 21299651
Submission date Dec 07, 2010
Last update date Mar 22, 2012
Contact name Andre Nantel
Phone 514-496-6370
Fax 514-496-9127
Organization name National Research Council of Canada
Department Biotechnology Research Institute
Street address 6100 Royalmount
City Montreal
State/province QC
ZIP/Postal code H4P 2R2
Country Canada
Platforms (1)
GPL9818 NRC-BRI C. albicans expression microarray V2.0
Samples (4)
GSM635588 delta-ccr4 Replicate1
GSM635589 delta-ccr4 Replicate2
GSM635590 delta-ccr4 Replicate3
BioProject PRJNA135877

Download family Format
SOFT formatted family file(s) SOFTHelp
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Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE25891_RAW.tar 5.8 Mb (http)(custom) TAR (of TXT)
Processed data included within Sample table

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