Cited by 189Mitochondrial Function and PathologyAutophagy in Disease and TherapyGenomics, phytochemicals, and oxidative stress

Lipopolysaccharide Stimulates Mitochondrial Biogenesis via Activation of Nuclear Respiratory Factor-1

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Suliman, Hagir B., Carraway, Martha S., Welty-Wolf, Karen E., Whorton, A.Richard, Piantadosi, Claude A.·2003·Journal of Biological Chemistry

Abstract

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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Crossref · 10.1074/jbc.m304719200

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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
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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