Happy to share the recent collaborative study of BioSIM (Tatiana F. Vieira and Sérgio F. Sousa) with researchers from the Universities of Minho and Bordeaux, published in FEBS Letters (IF 3.50). In this study, a combination of experimental and theoretical approaches was employed to investigate the mode of actionof cymoxanil as fungicide. The results led us to propose that CYM blocks the interaction of cytochrome c with CcO, hampering electron transfer and inhibiting CcO catalytic activity. Although other targets cannot be excluded, our data offer valuable insights into the mode of action of CYM that will be instrumental in driving informed management of the use of this fungicide.
The fungicide cymoxanil impairs respiration in Saccharomyces cerevisiae via cytochrome c oxidase inhibition
Filipa Mendes, Cátia Santos-Pereira, Tatiana F. Vieira, Mélanie Martins Pinto, Bruno B. Castro, Sérgio F. Sousa, Maria João Sousa, Anne Devin, and Susana R. Chaves
FEBS Letters (2024) | DOI: 10.1002/1873-3468.14907
Abstract:
Cymoxanil (CYM) is a widely used synthetic acetamide fungicide, but its biochemical mode of action remains elusive. Since CYM inhibits cell growth, biomass production, and respiration in Saccharomyces cerevisiae, we used this model to characterize the effect of CYM on mitochondria. We found it inhibits oxygen consumption in both whole cells and isolated mitochondria, specifically inhibiting cytochrome c oxidase (CcO) activity during oxidative phosphorylation. Based on molecular docking, we propose that CYM blocks the interaction of cytochrome c with CcO, hampering electron transfer and inhibiting CcO catalytic activity. Although other targets cannot be excluded, our data offer valuable insights into the mode of action of CYM that will be instrumental in driving informed management of the use of this fungicide.