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Interferons suppress mitochondrial gene transcription by depleting mitochondrial transcription factor A (mtTFA)
H Inagaki1, Y Matsushima, M Ohshima
1Graduate Program of Biochemical Regulation, Graduate School of Agricultural Sciences, Nagoya University, Japan.
Abstract:
Mitochondrial gene transcription activity in organello was suppressed after culturing HeLa cells with 1000 U/ml of interferon-alpha (IFN-alpha) or IFN-gamma for 18 h. The suppression was associated with reduced levels of mitochondrial gene transcripts. Northern blot analysis of HeLa cell RNA showed marked reduction of the mRNA encoding for mitochondrial transcription factor A (mtTFA). Immunoblotting with antiserum directed against recombinant mtTFA showed a reduced level of the protein as well. Consistently, gel-retardation assay of mitochondrial extract showed reduced level of functional mtTFA, which is known to bind to both heavy and light strand promoters of bidirectionally transcribed mitochondrial DNA. We suggest that depletion of mtTFA is a pathway through which IFNs depress the mitochondrial respiration.
Insights
Interferons (IFNs) suppress mitochondrial gene transcription by reducing mitochondrial transcription factor A (mtTFA) levels. This depletion of mtTFA impairs mitochondrial respiration.
Area of Science:
- Molecular Biology
- Cell Biology
- Immunology
Background:
- Interferons (IFNs) are crucial signaling molecules in the immune system.
- Mitochondria play a vital role in cellular energy production and are regulated by specific transcription factors.
Purpose of the Study:
- To investigate the effect of interferon-alpha (IFN-alpha) and interferon-gamma (IFN-gamma) on mitochondrial gene transcription in HeLa cells.
- To elucidate the underlying molecular mechanisms by which IFNs impact mitochondrial function.
Main Methods:
- HeLa cells were cultured with IFN-alpha or IFN-gamma.
- Mitochondrial gene transcription activity was assessed.
- Northern blot, immunoblotting, and gel-retardation assays were employed to analyze mitochondrial transcription factor A (mtTFA) mRNA and protein levels.
Main Results:
- IFN treatment significantly suppressed mitochondrial gene transcription and reduced mitochondrial gene transcripts.
- A marked reduction in both mRNA and protein levels of mitochondrial transcription factor A (mtTFA) was observed.
- Functional mtTFA, essential for mitochondrial DNA promoter binding, was found to be depleted.
Conclusions:
- Interferons (IFNs) suppress mitochondrial gene transcription through the depletion of mitochondrial transcription factor A (mtTFA).
- Reduced mtTFA levels are a key pathway through which IFNs depress mitochondrial respiration.