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| 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.
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| Overall design |
Two-color experimental design comparing cells with a double-knockout of the CCR4 genes to cells with a reintegrated CCR4 gene.
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| 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 |
| E-mail(s) |
andre.nantel@nrc-cnrc.gc.ca
|
| Phone |
514-496-6370
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| 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 |
| |
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| Platforms (1) |
| GPL9818 |
NRC-BRI C. albicans expression microarray V2.0 |
|
| Samples (4)
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| Relations |
| BioProject |
PRJNA135877 |
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