Nuclear Respiratory Factor 1 Regulates All Ten Nuclear-encoded Subunits of Cytochrome c Oxidase in Neurons
Open accessAbstract
Cytochrome c oxidase (COX) is one of only four bigenomic proteins in mammalian cells, having ten subunits encoded in the nuclear genome and three in the mitochondrial DNA. The mechanism of its bigenomic control is not well understood. The ten nuclear subunits are on different chromosomes, and the possibility of their coordinate regulation by the same transcription factor(s) deserves serious consideration. The present study tested our hypothesis that nuclear respiratory factor 1 (NRF-1) serves such a role in subunit coordination. Following in silico analysis of murine nuclear-encoded COX subunit promoters, electrophoretic mobility shift and supershift assays indicated NRF-1 binding to all ten promoters. In vivo chromatin immunoprecipitation assays also showed NRF-1 binding to all ten promoters in murine neuroblastoma cells. Site-directed mutagenesis of putative NRF-1 binding sites confirmed the functionality of NRF-1 binding on all ten COX promoters. These sites are highly conserved among mice, rats, and humans. Silencing of NRF-1 with RNA interference reduced all ten COX subunit mRNAs and mRNAs of other genes involved in mitochondrial biogenesis. We conclude that NRF-1 plays a significant role in coordinating the transcriptional regulation of all ten nuclear-encoded COX subunits in neurons. Moreover, NRF-1 is known to activate mitochondrial transcription factors A and B, thereby indirectly regulating the expressions of the three mitochondrial-encoded COX subunits. Thus, NRF-1…
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
These factors, including nuclear respiratory factor 1, nuclear factor erythroid-2-like 2, GA binding protein (nuclear respiratory factor 2), and Sp4, directly and indirectly control the expression of respiratory chain subunits encoded by nuclear and mitochondrial DNA.
“These factors, including nuclear respiratory factor 1, nuclear factor erythroid-2-like 2, GA binding protein (nuclear respiratory factor 2), and Sp4 [110–114] directly and indirectly control the expression of respiratory chain subunits encoded by nuclear and mitochondrial DNA [110, 115, 116].”
From Neuronal Apolipoprotein E4 Expression Results in Proteome-Wide Alterations and Compromises Bioenergetic Capacity by Disrupting Mitochondrial Function (2019) · cites this paper as [115]
Cites
Gleyzer, N., Vercauteren, K., & Scarpulla, R. C. (2005) · Molecular and Cellular Biology · doi:10.1128/mcb.25.4.1354-1366.2005 · Cited by 711 · see citing works
Nuclear control of respiratory gene expression in mammalian cells
Scarpulla, R. C. (2006) · Journal of Cellular Biochemistry · doi:10.1002/jcb.20743 · Cited by 489 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Glutamate Receptor Ion Channels: Structure, Regulation, and Function
Traynelis, S. F., Wollmuth, L. P., McBain, C. J., Menniti, F. S., Vance, K. M., Ogden, K. K., Hansen, K. B., Yuan, H., Myers, S. J., & Dingledine, R. (2010) · Pharmacological Reviews · doi:10.1124/pr.109.002451 · Cited by 3,568 · see citing works
Mitophagy and Quality Control Mechanisms in Mitochondrial Maintenance
Pickles, S., Vigié, P., & Youle, R. J. (2018) · Current Biology · doi:10.1016/j.cub.2018.01.004 · Cited by 2,081 · see citing works
Metabolic control of mitochondrial biogenesis through the PGC-1 family regulatory network
Scarpulla, R. C. (2011) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2010.09.019 · Cited by 1,281 · see citing works
Transcriptional integration of mitochondrial biogenesis
Scarpulla, R. C., Vega, R. B., & Kelly, D. P. (2012) · Trends in Endocrinology & Metabolism · doi:10.1016/j.tem.2012.06.006 · Cited by 798 · see citing works
Mitonuclear communication in homeostasis and stress
Quirós, P. M., Mottis, A., & Auwerx, J. (2016) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm.2016.23 · Cited by 787 · see citing works
Andrews, Z. B., Erion, D., Beiler, R., Liu, Z.-W., Abizaid, A., Zigman, J., Elsworth, J. D., Savitt, J. M., DiMarchi, R., Tschöp, M., et al. (2009) · The Journal of Neuroscience · doi:10.1523/jneurosci.3890-09.2009 · Cited by 289 · see citing works
Locus coeruleus cellular and molecular pathology during the progression of Alzheimer’s disease
Kelly, S. C., He, B., Perez, S. E., Ginsberg, S. D., Mufson, E. J., & Counts, S. E. (2017) · Acta Neuropathologica Communications · doi:10.1186/s40478-017-0411-2 · Cited by 286 · see citing works
Jamwal, S., Blackburn, J. K., & Elsworth, J. D. (2021) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2020.107705 · Cited by 236 · see citing works
Orr, A. L., Kim, C., Jimenez-Morales, D., Newton, B. W., Johnson, J. R., Krogan, N. J., Swaney, D. L., & Mahley, R. W. (2019) · Journal of Alzheimer's Disease · doi:10.3233/jad-181184 · Cited by 103 · see citing works
Priya, A., Johar, K., & Wong-Riley, M. T. T. (2013) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2013.07.002 · Cited by 33 · see citing works
Self-citation
- Authors
- Dhar, S. S., Ongwijitwat, S., & Wong-Riley, M. T. T.
- Affiliations
- Medical College of Wisconsin (US)
- ORCID
- Dhar, Shilpa S.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2008-02
- Volume
- 283
- Issue
- 6
- Pages
- 3120-3129
- ISSN
- 0021-9258 (ISSN-L)
- PMC
- PMC2669777
- OpenAlex
- W2113716558
- Cited by
- 188
- References
- 2
- Citations by year
- 2026: 4 · 2025: 6 · 2024: 5 · 2023: 7 · 2022: 11 · 2021: 9 · 2020: 21 · 2019: 9 · 2018: 7 · 2017: 9 · 2016: 10 · 2015: 8 · 2014: 9 · 2013: 12 · 2012: 19
- FWCI
- 4.07
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Eye Institute (R01EY005439, R01EY018441)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics, phytochemicals, and oxidative stress
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nuclear Receptors and Signaling
- Keywords
- NRF1, cytochrome c oxidase, nuclear-encoded subunits, transcriptional regulation, promoter binding, neurons, mitochondrial biogenesis, Nrf2, neuroblastoma cells, RNA interference
- MeSH terms
- Animals, Base Sequence, Cell Nucleus, Electron Transport Complex IV, DNA, Mitochondrial, Gene Expression Regulation, Humans, Molecular Sequence Data, Neurons, RNA, Messenger, Mutagenesis, Cell Line, Tumor, Nuclear Respiratory Factor 1, Mice, Rats
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
