Cited by 393Mitochondrial Function and PathologyRedox biology and oxidative stressMetabolism, Diabetes, and Cancer

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Role for Mitochondrial Oxidants as Regulators of Cellular Metabolism

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Nemoto, Shino, Takeda, Kazuyo, Yu, Zu-Xi, Ferrans, Victor J., Finkel, Toren·2000·Molecular and Cellular Biology

DOI 10.1128/mcb.20.19.7311-7318.2000PMC PMC86285

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Abstract

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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Authors: Nemoto, S., Takeda, K., Yu, Z.-X., Ferrans, V. J., & Finkel, T.
Affiliations: National Institutes of Health (US)
ORCID: Nemoto, Shino
Yu, Zu-Xi
Finkel, Toren
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
DOI: 10.1128/mcb.20.19.7311-7318.2000
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
Licence: journals.asm.org/non-commercial-tdm-license (tdm)
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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