The DOI matches its Crossref record; 42 of the 42 references it cites were found in a registry or an index.
Role for Mitochondrial Oxidants as Regulators of Cellular Metabolism
Open accessAbstract
Leakage of mitochondrial oxidants contributes to a variety of harmful conditions ranging from neurodegenerative diseases to cellular senescence. We describe here, however, a physiological and heretofore unrecognized role for mitochondrial oxidant release. Mitochondrial metabolism of pyruvate is demonstrated to activate the c-Jun N-terminal kinase (JNK). This metabolite-induced rise in cytosolic JNK1 activity is shown to be triggered by increased release of mitochondrial H(2)O(2). We further demonstrate that in turn, the redox-dependent activation of JNK1 feeds back and inhibits the activity of the metabolic enzymes glycogen synthase kinase 3beta and glycogen synthase. As such, these results demonstrate a novel metabolic regulatory pathway activated by mitochondrial oxidants. In addition, they suggest that although chronic oxidant production may have deleterious effects, mitochondrial oxidants can also function acutely as signaling molecules to provide communication between the mitochondria and the cytosol.
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“The impairment of mitochondrial ETC activity in mitochondrial metabolism leads to an increase of reactive oxygen species (ROS) production which occurs mainly at Complex I and Complex III [31].”
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Normalizing mitochondrial superoxide production blocks three pathways of hyperglycaemic damage
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Self-citationMitogenic Signaling Mediated by Oxidants in Ras-Transformed Fibroblasts
Irani, K., Xia, Y., Zweier, J. L., Sollott, S. J., Der, C. J., Fearon, E. R., Sundaresan, M., Finkel, T., & Goldschmidt-Clermont, P. J. (1997) · Science · doi:10.1126/science.275.5306.1649 · Cited by 1,588
Self-citationCell transformation by the superoxide-generating oxidase Mox1
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Epidermal Growth Factor (EGF)-induced Generation of Hydrogen Peroxide
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Oxidants, oxidative stress and the biology of ageing
Finkel, T., & Holbrook, N. J. (2000) · Nature · doi:10.1038/35041687 · Cited by 9,413
Self-citationMitochondria, Oxidants, and Aging
Balaban, R. S., Nemoto, S., & Finkel, T. (2005) · Cell · doi:10.1016/j.cell.2005.02.001 · Cited by 4,388
Self-citationPhysiological Roles of Mitochondrial Reactive Oxygen Species
Sena, L. A., & Chandel, N. S. (2012) · Molecular Cell · doi:10.1016/j.molcel.2012.09.025 · Cited by 2,632
Signal transduction by reactive oxygen species
Finkel, T. (2011) · Journal of Cell Biology · doi:10.1083/jcb.201102095 · Cited by 2,322
Self-citationCellular mechanisms and physiological consequences of redox-dependent signalling
Holmström, K. M., & Finkel, T. (2014) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3801 · Cited by 2,093
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Metadata
- Authors
- Nemoto, S., Takeda, K., Yu, Z.-X., Ferrans, V. J., & Finkel, T.
- Affiliations
- National Institutes of Health (US)
- Venue
- Molecular and Cellular Biology
- Publisher
- Informa UK Limited
- Published
- 2000-10-15
- Volume
- 20
- Issue
- 19
- Pages
- 7311-7318
- ISSN
- 0270-7306 (ISSN-L)
- 1098-5549
- PMC
- PMC86285
- OpenAlex
- W2123273404
- Cited by
- 393
- References
- 42
- Citations by year
- 2026: 1 · 2025: 5 · 2024: 6 · 2023: 9 · 2022: 9 · 2021: 15 · 2020: 12 · 2019: 21 · 2018: 12 · 2017: 12 · 2016: 17 · 2015: 18 · 2014: 17 · 2013: 10 · 2012: 19
- FWCI
- 5.66
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Molecular and Cellular Biology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Keywords
- hydrogen peroxide, c-Jun N-terminal kinase, JNK1, glycogen synthase kinase-3β, glycogen synthase, redox signaling, metabolic regulation, oxidative stress
- MeSH terms
- Animals, Antimycin A, Cells, Cultured, Cytosol, Endothelium, Vascular, Energy Metabolism, Enzyme Activation, Feedback, Glycogen Synthase, HeLa Cells, Humans, Hydrogen Peroxide, Kidney, Mitochondria, Neoplasm Proteins, Oxidation-Reduction, Umbilical Veins, 3T3 Cells, Oxidants, Reactive Oxygen Species, Calcium-Calmodulin-Dependent Protein Kinases, Muscle, Skeletal, Pyruvic Acid, Ribosomal Protein S6 Kinases, Mitogen-Activated Protein Kinases, MAP Kinase Signaling System, Glycogen Synthase Kinases, Glycogen Synthase Kinase 3, JNK Mitogen-Activated Protein Kinases, Mice
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