Cell wall integrity is linked to mitochondria and phospholipid homeostasis in Candida albicans through the activity of the post‐transcriptional regulator Ccr4‐Pop2

Department of Anatomy and Cell Biology, McGill University, Montreal, QC, Canada
Molecular Microbiology (Impact Factor: 4.42). 12/2010; 79(4):968 - 989. DOI: 10.1111/j.1365-2958.2010.07503.x


The cell wall is essential for viability of fungi and is an effective drug target in pathogens such as Candida albicans. The contribution of post-transcriptional 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 that 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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Available from: Thusitha Rupasinghe, Jan 22, 2014
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    • "Studies in C. albicans support the S. cerevisiae data. Mutations in CCR4, CAF1/POP2, NOT1, NOT3, and NOT5 give rise to cells that are defective in transitioning from yeast to hyphal growth (Cheng et al., 2003; Epp et al., 2010; Dagley et al., 2011). Substrate adherence and hyphal growth are important for the formation of C. albicans biofilms (Finkel and Mitchell, 2011). "
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    Full-text · Article · Dec 2013 · Frontiers in Genetics
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    • "The authors find that inositol pyrophosphates affect mitochondrial function and fermentation rates to control cellular ATP content. This suggests that pHc, inositol pyrophosphates and mitochondria function in an interdependent network to control cell division, resource distribution, and therefore potentially the balance between growth and cellular robustness [53-57]. "
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    • "Hypoxia would impact on mitochondrial function. Mitochondrial function is important for cell wall integrity in several fungal species, including S. cerevisiae, C. albicans and C. glabrata [41], [42], [43], [44], [45]; reviewed in [46]). In some cases, links between mitochondrial activity and cell wall ß-glucans have been reported [41], [43]. "
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