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Control of Mitochondrial Transcription Specificity Factors (TFB1M and TFB2M) by Nuclear Respiratory Factors (NRF-1 and NRF-2) and PGC-1 Family Coactivators
Open accessAbstract
In vertebrates, mitochondrial DNA (mtDNA) transcription is initiated bidirectionally from closely spaced promoters, HSP and LSP, within the D-loop regulatory region. Early studies demonstrated that mtDNA transcription requires mitochondrial RNA polymerase and Tfam, a DNA binding stimulatory factor that is required for mtDNA maintenance. Recently, mitochondrial transcription specificity factors (TFB1M and TFB2M), which markedly enhance mtDNA transcription in the presence of Tfam and mitochondrial RNA polymerase, have been identified in mammalian cells. Here, we establish that the expression of human TFB1M and TFB2M promoters is governed by nuclear respiratory factors (NRF-1 and NRF-2), key transcription factors implicated in mitochondrial biogenesis. In addition, we show that NRF recognition sites within both TFB promoters are required for maximal trans activation by the PGC-1 family coactivators, PGC-1alpha and PRC. The physiological induction of these coactivators has been associated with the integration of NRFs and other transcription factors in a program of mitochondrial biogenesis. Finally, we demonstrate that the TFB genes are up-regulated along with Tfam and either PGC-1alpha or PRC in cellular systems where mitochondrial biogenesis is induced. Moreover, ectopic expression of PGC-1alpha is sufficient to induce the coordinate expression of all three nucleus-encoded mitochondrial transcription factors along with nuclear and mitochondrial respiratory subunits. These results support the conclusion that the coordinate regulation of nucleus-encoded mitochondrial transcription factors by NRFs and PGC-1 family coactivators is essential to the control of mitochondrial biogenesis.
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“Key in orchestrating this process is the nuclear-encoded mitochondrial transcription factor A (TFAM), which is pivotal in regulating mtDNA transcription by directly interacting with mitochondrial genome along with mitochondrial transcription specificity factors TFB1M and TFB2M (Figure 3; Gleyzer et al., 2005; Ljubicic et al., 2010).”
From Mitochondrial (Dys)function and Insulin Resistance: From Pathophysiological Molecular Mechanisms to the Impact of Diet (2019) · cites this paper as Gleyzer et al., 2005
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MITOCHONDRIAL DNA MAINTENANCE IN VERTEBRATES
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Metadata
- Authors
- Gleyzer, N., Vercauteren, K., & Scarpulla, R. C.
- Affiliations
- Northwestern University (US)
- Corresponding author
- Scarpulla, Richard C.
- Venue
- Molecular and Cellular Biology
- Publisher
- Informa UK Limited
- Published
- 2005-02-01
- Volume
- 25
- Issue
- 4
- Pages
- 1354-1366
- ISSN
- 0270-7306 (ISSN-L)
- 1098-5549
- PMC
- PMC548005
- OpenAlex
- W2158088166
- Cited by
- 711
- References
- 39
- Citations by year
- 2026: 26 · 2025: 44 · 2024: 38 · 2023: 46 · 2022: 45 · 2021: 40 · 2020: 40 · 2019: 39 · 2018: 43 · 2017: 27 · 2016: 27 · 2015: 34 · 2014: 22 · 2013: 33 · 2012: 32
- FWCI
- 10.08
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Molecular and Cellular Biology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- U.S. Public Health Service
- National Institute of General Medical Sciences (GM32525-22, R56GM032525, R01GM032525)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Health Sciences › Medicine › Physiology (medical) › Adipose Tissue and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Keywords
- TFB1M, TFB2M, nuclear respiratory factors, NRF1, Nrf2, PGC-1α, mitochondrial biogenesis, mitochondrial transcription, TFAM, transcriptional regulation, mitochondrial RNA polymerase
- MeSH terms
- Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha, Animals, Base Sequence, DNA-Binding Proteins, DNA, Mitochondrial, High Mobility Group Proteins, Humans, Methyltransferases, Molecular Sequence Data, Nuclear Proteins, Promoter Regions, Genetic, Transcription Factors, Trans-Activators, Up-Regulation, Mitochondrial Proteins, Electrophoretic Mobility Shift Assay, BALB 3T3 Cells, 3T3-L1 Cells, Nuclear Respiratory Factors, NF-E2-Related Factor 1, Nuclear Respiratory Factor 1, NF-E2-Related Factor 2, Mice
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