Transcription factor NF-kappa B represses ANT1 transcription and leads to mitochondrial dysfunctions
Open accessAbstract
Mitochondria are intracellular organelles involved in cell survival and death, and dysfunctions of mitochondria are related to neurodegenerative diseases. As the most abundant protein in the mitochondrial inner membrane, adenine nucleotide translocator 1 (ANT1) plays a critical role in mitochondrial function, including the exchange of adenosine triphosphate/adenosine diphosphate (ATP/ADP) in mitochondria, basal proton leak and mitochondrial permeability transition pore (mPTP). Here, we show that ANT1 transcription is regulated by transcription factor NF-kappa B (NF-κB). NF-κB is bound to two NF-κB responsive elements (NREs) located at +1 to +20 bp and +41 to +61 bp in the ANT1 promoter. An NF-κB signalling stimulator, tumour necrosis factor alpha (TNFα), suppresses ANT1 mRNA and protein expression. Activation of NF-κB by TNFα impairs ATP/ADP exchange and decreases ATP production in mitochondria. Activation of NF-κB by TNFα decreases calcium induced mPTP opening, elevates mitochondrial potential and increases reactive oxygen species (ROS) production in both T98G human glioblastoma cells and rat cortical neurons. These results demonstrate that NF-κB signalling may repress ANT1 gene transcription and impair mitochondrial functions.
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Activated NFkB can bind to two response elements within the gene promoter of ANT-1, resulting in reduced expression and concomitant decline in mitochondrial ATP production in human glioblastoma cells.
“recent work in human glioblastoma cells has highlighted that activated NFkB can bind to two response elements within the gene promoter of the ADP/ATP translocase, ANT-1, resulting in its reduced expression and concomitant decline in mitochondrial ATP production [48].”
From Proinflammatory NFkB signalling promotes mitochondrial dysfunction in skeletal muscle in response to cellular fuel overloading (2019) · cites this paper as [48]
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Reactive Oxygen Species in Metabolic and Inflammatory Signaling
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“Indeed, the activation of NFκB signaling in cells exposed to TNFα leads to reduced ANT-1 mRNA and protein expression and to an increase in H2O2 generation [157].”
BackgroundNisr, R. B., Shah, D. S., Ganley, I. G., & Hundal, H. S. (2019) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-019-03148-8 · Cited by 142 · see citing works
- Authors
- Zhang, C., Jiang, H., Wang, P., Liu, H., & Sun, X.
- Affiliations
- Qilu Hospital of Shandong University (CN)
- Shandong University (CN)
- Corresponding author
- Sun, Xiulian
- Venue
- Scientific Reports
- Published
- 2017-03-20
- Volume
- 7
- Issue
- 1
- Pages
- 44708-44708
- ISSN
- 2045-2322 (ISSN-L)
- PMC
- PMC5357787
- OpenAlex
- W2602809814
- Cited by
- 37
- References
- 57
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 5 · 2023: 1 · 2022: 3 · 2021: 7 · 2020: 8 · 2019: 5 · 2018: 5
- FWCI
- 2.01
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Scientific Reports (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (81322014)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Keywords
- NF-κB, ANT1, transcriptional repression, mitochondrial dysfunction, TNF-α, promoter regulation, ADP/ATP exchange, mitochondrial permeability transition pore, reactive oxygen species, mitochondrial membrane potential, glioblastoma cells, cortical neurons, neurodegenerative diseases
- MeSH terms
- Mitochondrial Permeability Transition Pore, Adenosine Diphosphate, Adenosine Triphosphate, Base Sequence, Calcium, Humans, Mitochondria, Promoter Regions, Genetic, Transcription, Genetic, NF-kappa B, Reactive Oxygen Species, Response Elements, Mitochondrial Membrane Transport Proteins, Adenine Nucleotide Translocator 1, Membrane Potential, Mitochondrial, HEK293 Cells
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