Increase in intracellular hydrogen peroxide and upregulation of a nuclear respiratory gene evoked by impairment of mitochondrial electron transfer in human cells.
We have investigated an interorganelle communication pathway between the nucleus and mitochondria. We loaded a stress specific to mitochondria of human fibroblast cells by antimycin A (AA), an inhibitor of the mitochondrial cytochrome bc1 complex. AA inhibited cellular respiration in a dose-dependent manner. When the respiratory capacity was reduced to 50-70% of the original one, mRNA levels of cytochrome c1 as well as cytochrome b increased at 24 h after AA treatment, resulting in maintenance of the cell viability. In contrast, the cells retaining less than 40% of the original capacity showed no increase in either mRNA level and were targeted for death. Intracellular H2O2 level monitored by the fluorescence of dichlorofluorescein increased within 3 h in both the cases, although this increase was higher in the cells where the mRNA levels increased. An antioxidant N-acetylcysteine repressed the increases of not only H2O2 but also cytochrome c1 mRNA levels. These results suggest that the cells can respond to a limited impairment of electron transfer by promoting expression of nuclear and mitochondrial genes, probably through an H2O2-dependent signaling pathway.
Suzuki
H
H
Laboratory of Molecular Biology and Biotechnology, Fukui Prefectural University, 4-1-1 Kenjojima, Matsuoka-cho, Yoshida-gun, Fukui, 9101195, Japan.
Kumagai
T
T
Goto
A
A
Sugiura
T
T
D000111:Acetylcysteine / Q000494:pharmacology; D000968:Antimycin A / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology; D016923:Cell Death; D002461:Cell Line, Transformed; D002467:Cell Nucleus / Q000235:genetics; D003573:Cytochrome b Group / Q000235:genetics*; D003575:Cytochromes c1 / Q000235:genetics*; D004579:Electron Transport; D005456:Fluorescent Dyes; D005786:Gene Expression Regulation; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction
D000975:Antioxidants; D003573:Cytochrome b Group; D005456:Fluorescent Dyes; D012333:RNA, Messenger; D000968:Antimycin A; D003575:Cytochromes c1; D006861:Hydrogen Peroxide; D000111:Acetylcysteine