Functional Study Of The Mitochondrial Proteins Yar068Wp/Yhr214W-Ap

Antifungal drug resistance has become an increasing problem. Since ergosterol is the unique lipid composition of fungal plasma membrane (cholesterol of mammalian plasma membrane), it has been the best target for designning antifungal drug.Pdr5p is a vital ABC transporter in yeast, showing notable reduced resistance to azole drugs while deletion. Our previous results illustrated Pdr5p relates with ergosterol homeostasis and PDR5deletion reduces percentage composition of ergosterol in plasma membrane.This thesis found a pair of unknown function homologous proteins associated with Pdr5p, Yar068Wp/Yhr214W-Ap, whose expression level are negatively correlated with PDR5. Our research indicates that Yar068Wp and Yhr214W-Ap locate to mitochondria, with3prediction transmembrane helix (TMH), of which TMH1and TMH2are vital for its location. The expression level of YAR068W/YHR214W-A positively correlates with the resistance of AmB, and negatively correlates with resistance of azole drugs. Since the resistance of AmB and azole drugs is affected by ergosterol, we firstly proved that the mitochondria protein Yar068Wp/Yhr214W-Ap could influence ergosterol homeostasis, and then the drug resistance. After Yar068Wp/Yhr214W-Ap were disrupted, there is a significant reduction in heme content of cytoplasm, implying Yar068Wp/Yhr214W-Ap may influence ergosterol homeostasis by affecting the Heme homeostasis.Our results firstly reveals the connection between mitochondria protein Yar068Wp/Yhr214W-Ap、ABC transporter Pdr5p and cellullar ergosterol. It has strong innovation and could supply new theoretical foundation for designing anti-fungal drugs.