Activation of the human mitochondrial transcriptionfactor A gene by nuclear respiratory factors: a potential regulatory linkbetween nuclear and mitochondrial gene expression in organellebiogenesis.
Open accessAbstract
Mitochondrial transcription factor A (mtTFA), the product of a nuclear gene, stimulates transcription from the two divergent mitochondrial promoters and is likely the principal activator of mitochondrial gene expression in vertebrates. Here we establish that the proximal promoter of the human mtTFA gene is highly dependent upon recognition sites for the nuclear respiratory factors, NRF-1 and NRF-2, for activity. These factors have been previously implicated in the activation of numerous nuclear genes that contribute to mitochondrial respiratory function. The affinity-purified factors from HeLa cells specifically bind to the mtTFA NRF-1 and NRF-2 sites through guanine nucleotide contacts that are characteristic for each site. Mutations in these contacts eliminate NRF-1 and NRF-2 binding and also dramatically reduce promoter activity in transfected cells. Although both factors contribute, NRF-1 binding appears to be the major determinant of promoter function. This dependence on NRF-1 activation is confirmed by in vitro transcription using highly purified recombinant proteins that display the same binding specificities as the HeLa cell factors. The activation of the mtTFA promoter by both NRF-1 and NRF-2 therefore provides a link between the expression of nuclear and mitochondrial genes and suggests a mechanism for their coordinate regulation during organelle biogenesis.
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PGC-1α indirectly regulates mtDNA expression by increasing transcription of Tfam and NRF1.
“PGC-1α is also indirectly involved in regulating the expression of mitochondrial DNA (mtDNA) by increasing the transcription of mitochondrial transcription factor A (Tfam) and nuclear respiratory factor 1 (NRF1) [92].”
From Potential Roles of n-3 PUFAs during Skeletal Muscle Growth and Regeneration (2018) · cites this paper as [92]
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- Authors
- Virbasius, J. V., & Scarpulla, R. C.
- Affiliations
- Northwestern University (US)
- ORCID
- Virbasius, J V
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 1994-02-15
- Volume
- 91
- Issue
- 4
- Pages
- 1309-1313
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC43147
- OpenAlex
- W2002662437
- Cited by
- 819
- References
- 27
- Citations by year
- 2026: 20 · 2025: 16 · 2024: 44 · 2023: 44 · 2022: 38 · 2021: 48 · 2020: 56 · 2019: 30 · 2018: 30 · 2017: 27 · 2016: 26 · 2015: 34 · 2014: 23 · 2013: 15 · 2012: 31
- FWCI
- 5.83
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of General Medical Sciences (GM 32525-10)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics, phytochemicals, and oxidative stress
- Keywords
- TFAM, NRF1, Nrf2, nuclear respiratory factors, promoter activation, mitochondrial gene expression, organelle biogenesis, guanine nucleotide binding, transcriptional regulation, HeLa cells
- MeSH terms
- Base Sequence, Cell Compartmentation, Cell Nucleus, DNA Mutational Analysis, DNA-Binding Proteins, Gene Expression Regulation, HeLa Cells, Humans, Mitochondria, Molecular Sequence Data, Nuclear Proteins, Promoter Regions, Genetic, Protein Binding, Recombinant Fusion Proteins, Transcription Factors, Chloramphenicol O-Acetyltransferase, Trans-Activators, Mitochondrial Proteins, Nuclear Respiratory Factors, NF-E2-Related Factor 1, Nuclear Respiratory Factor 1, GA-Binding Protein Transcription Factor
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