Lipopolysaccharide Stimulates Mitochondrial Biogenesis via Activation of Nuclear Respiratory Factor-1
Open accessAbstract
Exposure to bacterial lipopolysaccharide (LPS) in vivo damages mitochondrial DNA (mtDNA) and interferes with mitochondrial transcription and oxidative phosphorylation (OXPHOS). Because this damage accompanies oxidative stress and is reversible, we postulated that LPS stimulates mtDNA replication and mitochondrial biogenesis via expression of factors responsive to reactive oxygen species, i.e. nuclear respiratory factor-1 (NRF-1) and mitochondrial transcription factor-A. In testing this hypothesis in rat liver, we found that LPS induces NRF-1 protein expression and activity accompanied by mRNA expression for mitochondrial transcription factor-A, mtDNA polymerase gamma, NRF-2, and single-stranded DNA-binding protein. These events restored the loss in mtDNA copy number and OXPHOS gene expression caused by LPS and increased hepatocyte mitotic index, nuclear cyclin D1 translocation, and phosphorylation of pro-survival kinase, Akt. Thus, NRF-1 was implicated in oxidant-mediated mitochondrial biogenesis to provide OXPHOS for proliferation. This implication was tested in novel mtDNA-deficient cells generated from rat hepatoma cells that overexpress NRF-1. Depletion of mtDNA (rhoo clones) diminished oxidant production and caused loss of NRF-1 expression and growth delay. NRF-1 expression and growth were restored by exogenous oxidant exposure indicating that oxidative stress stimulates biogenesis in part via NRF-1 activation and corresponding to recovery events after LPS-induced liver damage.
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NOX1 is expressed in VSMCs and in lower levels is also found in ECs.
“The isoform NOX1 is expressed in VSMCs and in lower levels is also found in ECs (556, 909) (FIGURE 9, Table 5).”
From Sources of Vascular Nitric Oxide and Reactive Oxygen Species and Their Regulation (2019) · cites this paper as [909]
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- Authors
- Suliman, H. B., Carraway, M. S., Welty-Wolf, K. E., Whorton, A. R., & Piantadosi, C. A.
- Affiliations
- Duke University (US)
- Duke Medical Center (US)
- Corresponding author
- Piantadosi, Claude A.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2003-10
- Volume
- 278
- Issue
- 42
- Pages
- 41510-41518
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2086283039
- Cited by
- 189
- References
- 58
- Citations by year
- 2026: 1 · 2025: 7 · 2024: 1 · 2023: 7 · 2022: 5 · 2021: 9 · 2020: 6 · 2019: 4 · 2018: 7 · 2017: 5 · 2016: 6 · 2015: 9 · 2014: 9 · 2013: 6 · 2012: 15
- FWCI
- 2.30
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics, phytochemicals, and oxidative stress
- Keywords
- lipopolysaccharide, mitochondrial biogenesis, NRF1, TFAM, mitochondrial DNA replication, oxidative phosphorylation, oxidative stress, reactive oxygen species, hepatocytes, Akt signaling, cyclin D1, liver injury, bacterial endotoxin
- MeSH terms
- Animals, Cell Division, Cell Nucleus, DNA-Binding Proteins, DNA, Mitochondrial, Lipopolysaccharides, Liver, Male, Membrane Potentials, Mitochondria, Mutation, Oxygen, Phosphorylation, Proto-Oncogene Proteins, RNA, Messenger, Time Factors, Blotting, Southern, Trans-Activators, Polymerase Chain Reaction, Oxidants, Rats, Sprague-Dawley, Protein Serine-Threonine Kinases, Reactive Oxygen Species, Oxidative Stress, Cyclin D1, Reverse Transcriptase Polymerase Chain Reaction, Protein Transport, Active Transport, Cell Nucleus, Proto-Oncogene Proteins c-akt, Nuclear Respiratory Factors, NF-E2-Related Factor 1, Nuclear Respiratory Factor 1, Rats
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