Fluconazole toxicity is independent of oxidative stress and apoptotic effector mechanisms in Saccharomyces cerevisiae.
Fluconazole toxicity was previously shown to require intact mitochondria in Saccharomyces cerevisiae, however, the mechanism of mitochondrial-dependent azole toxicity is unclear. Here we show that fluconazole toxicity is not attenuated by the overexpression of the mitochondrially-acting human antiapoptotic protein Bcl-2 nor is it increased by the presence of the oxidating agents in S. cerevisiae. Our data further support the notion that mitochondrial toxicity in the presence of azoles is modulated by the conversion of ergosterol precursors to toxic sterols.
Kontoyiannis
D P
DP
Department of Infectious Diseases, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA. dkontoyi@mdanderson.org
Murray
P J
PJ
D017209:Apoptosis; D015725:Fluconazole / Q000494:pharmacology*; D008928:Mitochondria / Q000378:metabolism; D018384:Oxidative Stress; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis / Q000235:genetics; D012441:Saccharomyces cerevisiae / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D014162:Transfection
D019253:Proto-Oncogene Proteins c-bcl-2; D015725:Fluconazole