Protective effects of ETC complex III and cytochrome c against hydrogen peroxide-induced apoptosis in yeast.
In mammals, the mitochondrial electron transfer components (ETC) complex III and cytochrome c (cyt c) play essential roles in reactive oxygen species (ROS)-induced apoptosis. However, in yeast, the functions of cyt c and other ETC components remain unclear. In this study, three ETC-defective yeast mutants qcr7Δ, cyc1Δcyc7Δ, and cox12Δ, lacking cyt c oxidoreductase (complex III), cyt c, and cyt c oxidase (complex IV), respectively, were used to test the roles of these proteins in the response of cells to hydrogen peroxide (H₂O₂). Mutants qcr7Δ and cyc1Δcyc7Δ displayed greater H₂O₂ sensitivity than the wild-type or cox12Δ mutant. Consistent with this, qcr7Δ and cyc1Δcyc7Δ produced higher ROS levels, displayed derepressed expression of the proapoptotic genes AIF1, NUC1, and NMA111, but not YCA1, at the mRNA level, and were more vulnerable to H₂O₂-induced apoptosis. Interestingly, mutants lacking these proapoptotic genes displayed enhanced H₂O₂ tolerance, but unaffected ROS accumulation. Furthermore, the overexpression of antiapoptotic genes (Bcl-2, Ced-9, AtBI-1, and PpBI-1) reduced the levels of AIF1, NUC1, and NMA111 mRNAs, and reduced H₂O₂-induced cell death. Our findings identify two ETC components as early-inhibitory members of the ROS-mediated apoptotic pathway, suggesting their essential roles in metabolizing H₂O₂, probably by providing reduced cyt c, allowing cyt c peroxidase to remove H₂O₂ from the cells.
Institute of Genetics, Key Laboratory for Cell and Gene Engineering of Zhejiang Province, College of Life Sciences, Zhejiang University , Hangzhou , P. R. China.
Chao-qun
CQ
Wang
Xuan
X
Li
Ming-qiang
MQ
Wang
Jia
J
Qian
Ke
K
Zheng
Hong-wu
HW
Bian
Ning
N
Han
Jun-hui
JH
Wang
Jian-wei
JW
Pan
Mu-yuan
MY
Zhu
D000818:Animals; D017209:Apoptosis; D016923:Cell Death / Q000187:drug effects*; D045304:Cytochromes c / Q000378:metabolism*; D014450:Electron Transport Complex III / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D017382:Reactive Oxygen Species; D015003:Yeasts
D017382:Reactive Oxygen Species; D045304:Cytochromes c; D006861:Hydrogen Peroxide; D014450:Electron Transport Complex III