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Inhibiting Roles Of ETC ComplexⅢand Cytochrome C In H2O2 Induced Apoptotic Pathway In Yeast

Posted on:2013-10-25Degree:MasterType:Thesis
Country:ChinaCandidate:C Q WangFull Text:PDF
GTID:2230330371469214Subject:Genetics
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In mammalian, reactive oxygen species (ROS) induce apoptosis and cytochrome c (cyt c), a component of electron transport chain (ETC), is an important mediator in the pathway. In yeast, however, functions of cyt c and other ETC component remain unclear. In this study, three ETC-defective yeast mutants qcr7A, cyclAcyc7△and cox12△, lacking cytochrome c oxidoreductase (complexⅢ), cyt c and cytochrome c oxidase (complex IV) respectively, were used to test their roles in response of cells to hydrogen peroxide (H2O2). Our results show that qcr7△and cycl△cyc7△displayed more H2O2 sensitivity, compared to wild-type (WT) and coxl2△. Consistently, qcr7△and cyclAcyc7A produced higher ROS levels, derepressed the expression of proapoptotic genes AIF1, NUC1 and NMA111, but not YCA1, at mRNA levels, and rendered cells more vulnerable to H2O2-induced apoptosis. Interestingly, the mutants lacking these proapoptotic genes enhance H2O2 tolerance, but had no effect on ROS accumulation. Furthermore, overexpression of antiapoptotic genes (Bcl-2, Ced-9, AtBI-1 and PpBI-1) suppressed the mRNA levels of AIF1, NUC1 and NMA111 (but not of YCA1) and reduced H2O2-induced cell death. Our findings identify two ETC components as early-inhibiting members in the ROS-mediated apoptotic pathway and antiapoptotic members block the late pathway through repressing proapoptotic members.
Keywords/Search Tags:Yeast, H2O2, Cytochrome c, Cytochrome c oxidoreductase, Cytochrome c oxidase, Apoptotic members, Antiapoptotic members
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