Protective effects of ETC complex III and cytochromecagainst hydrogen peroxide-induced apoptosis in yeast

Abstract

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.

The Rare Sugar Tagatose Differentially Inhibits the Growth of Phytophthora infestans and Phytophthora cinnamomi by Interfering With Mitochondrial Processes

“…The expression of nma111 was upregulated and downregulated by tagatose in P. infestans and P. cinnamomi, respectively, and its expression was previously linked to ROS accumulation in Saccharomyces spp. (Wang et al, 2014), demonstrating a strong connection of physiological effects and transcriptional changes observed in tagatose-incubated P. infestans and P. cinnamomi. Therefore, further transcriptomic and metabolomic studies are required, in order to better understand the species-specific response of Phytophthora spp.…”

Linkage mapping of yeast cross protection connects gene expression variation to a higher-order organismal trait

“…Intriguingly, the residual cross protection is also absent in the hybrid carrying the HAP1 S288c allele, suggesting the involvement of other genes depending upon the genetic background ( Fig 4B and 4C ). It is known that yeast strains with respiratory defects have increased ROS sensitivity [ 93 , 94 ], potentially due to increased programmed cell death [ 95 ]. It is possible that reduced respiratory activity and concomitant ROS sensitivity in strains lacking HAP1 is exacerbated by genetic interactions with other alleles.…”

Oncostatic-Cytoprotective Effect of Melatonin and Other Bioactive Molecules: A Common Target in Mitochondrial Respiration

“…In fact, it can generate local hypoxia and it can modulate the pO 2 , facts that could have also important implications for the survival of neoplastic cells. Moreover, the oxygen consumption and the generation of reactive oxygen species (ROS), and in particular hydrogen peroxide, play numerous roles in many pathways [ 113 , 114 , 115 , 116 , 117 , 118 ].…”

“…From a strictly evolutionary viewpoint, the endosymbiosis between archaebacteria and proto-eukaryotes, which led to the development of the existing mitochondria, is undoubtedly an essential step for the development of life. It is clear how these organelles, in addition to the energy question, have a key role in the management of aerobe life and how the mitochondrion can adjust pO 2 and in a sense functioning as a rheostat of oxygen tension, interfering on all signaling connected to it, such as those ROS mediated [ 113 , 114 , 115 , 116 , 117 , 118 ].…”