NRF-1: a trans-activator of nuclear-encoded respiratory genes in animal cells.
Open accessAbstract
The assembly of the respiratory apparatus requires the coordinate expression of a large number of genes from both nuclear and mitochondrial genetic systems. In vertebrate organisms, the molecular mechanisms integrating the activities of these distinct genomic compartments in response to tissue demands for respiratory energy remain unknown. A potential inroad to this problem came with the discovery of nuclear respiratory factor 1 (NRF-1), a novel transcriptional activator defined by mutational and DNA binding analysis of the somatic cytochrome c promoter. Functional NRF-1 sites are now observed in several other recently isolated nuclear genes whose products function in the mitochondria. Among these are genes encoding subunits of the cytochrome c oxidase (subunit VIc) and reductase (ubiquinone-binding protein) complexes. In addition, a functional NRF-1 site resides in the MRP RNA gene encoding the RNA moiety of a ribonucleoprotein endonuclease involved in mitochondrial DNA replication. Synthetic oligomers of these sites competitively displace NRF-1 binding to the cytochrome c promoter. NRF-1-binding activities for each site also have the same thermal lability, copurify chromatographically, and make similar guanosine nucleotide contacts within each recognition sequence. Moreover, NRF-1 recognition in vitro correlates with the ability of each site to stimulate expression in vivo from a truncated cytochrome c promoter. The presence of NRF-1-binding sites in nuclear genes encoding structural components of the mammalian electron transport chain, as well as the mitochondrial DNA replication machinery, suggests a mechanism for coordination of nuclear and mitochondrial genetic systems through the concerted modulation of nuclear genes.
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PGC1α co-activation of NRF1-mediated transcription leads to transcription and subsequent translocation of TFAM to the mitochondrion, thus increasing mtDNA transcription.
“PGC1␣ co-activation of NRF1-mediated transcription leads to transcription and subsequent translocation of TFAM to the mitochondrion, thus increasing mtDNA transcription (34,35).”
From A High-Fat Diet Coordinately Downregulates Genes Required for Mitochondrial Oxidative Phosphorylation in Skeletal Muscle (2005) · cites this paper as [34]
The Discussion identifies the nuclear gene for mitochondrial transcription factor 1 as a possible NRF-1 target and says the factor activates mitochondrial transcription. It presents NRF-1 regulation of that gene as a prediction, however, and does not describe PGC1α co-activation, TFAM translocation, or the claimed causal sequence. Page numbers are not available in our copy. (LLM, conf=0.86)
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- Authors
- Evans, M. J., & Scarpulla, R. C.
- Affiliations
- Northwestern University (US)
- ORCID
- Evans, M J
- Venue
- Genes & Development
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 1990-06
- Volume
- 4
- Issue
- 6
- Pages
- 1023-1034
- ISSN
- 0890-9369 (ISSN-L)
- 1549-5477
- OpenAlex
- W2042789770
- Cited by
- 417
- References
- 46
- Citations by year
- 2026: 5 · 2025: 8 · 2024: 11 · 2023: 19 · 2022: 20 · 2021: 18 · 2020: 7 · 2019: 11 · 2018: 13 · 2017: 14 · 2016: 7 · 2015: 16 · 2014: 4 · 2013: 9 · 2012: 13
- Type
- posted content
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Genes & Development (publishedVersion)
- PubMed (publishedVersion)
- Funders
- American Cancer Society
- Northwestern University
- National Institutes of Health
- U.S. Public Health Service
- National Institute of General Medical Sciences (GM32525, GM08061)
- 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
- NRF1, transcriptional activator, nuclear-encoded mitochondrial genes, mitochondrial DNA replication, electron transport chain, transcriptional regulation
- MeSH terms
- Animals, Base Sequence, Binding Sites, Binding, Competitive, Cell Line, Cytochrome c Group, Electron Transport Complex IV, Gene Expression Regulation, Genes, HeLa Cells, Humans, Mitochondria, Molecular Sequence Data, Promoter Regions, Genetic, Trans-Activators
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