Cell wall integrity is linked to mitochondria and phospholipid homeostasis in XXXX through the activity of the post-transcriptional regulator Ccr4-Pop2.

@entity5132 @entity375 @entity5637 @entity11794
The cell wall is essential for viability of fungi and is an effective drug target in pathogens such as @entity5132 . The contribution of post-transcriptional gene regulators to cell wall integrity in @entity5132 is unknown. We show that the @entity5132 Ccr4-Pop2 mRNA deadenylase, a regulator of mRNA stability and translation, is required for cell wall integrity. The ccr4/pop2 mutants display reduced wall b-glucans and sensitivity to the echinocandin @entity11794 . 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 @entity375 collection of mitochondrial mutants. We identify several mitochondrial proteins required for @entity11794 tolerance and find a connection between mitochondrial phospholipid homeostasis and @entity11794 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 @entity5132 also Sam37 is essential for @entity11794 tolerance. Our study provides the basis for an integrative view of mitochondrial function in fungal cell wall biogenesis and resistance to @entity5637 antifungal drugs.
