Bakers' Yeast, a Model System to Study Mutations Found in the Cytochrome B Q_0 Domain of Human and Crop Pathogens

摘要

The mitochondrial bc_1 complex is a membrane-bound enzyme that catalyses the transfer of electrons from ubiquinol to cytochrome c and couples this electron transfer to the vectorial translocation of proton across the inner mitochondrial membrane. Somebc_1 inhibitors are widely used in agriculture and medicine to control pathogens. Mutations in the mitochondrialry-encoded subunit of the enzyme, cytochrome b, causing, or presumed to cause, resistance to inhibitors have been reported in crop and in human pathogens. A detailed study of the effects of the mutations on the bc_1 activity is often hampered by the difficulty of genetically-modifying or even cultivating the pathogens. We have developed yeast Saccharomyces cerevisae as an alternative system to characterize the impact of the mutations. In this paper, we first review briefly the mutations observed in the Q_0 region of Pneumocystis carinii, and of Plasmodium sp, resistant to atovaquone, a bydroxynaphthoquinone that is used to treat some microbial infections in humans. We then focus on two mutations, Y279C and L275F. Finally we study the mutation G143A reported in resistant isolates from various crop pathogens.