Expression of UCP3 in CHO cells does not cause uncoupling, but controls mitochondrial activity in the presence of glucose
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The proton-transport activity of UCP1 (uncoupling protein 1) triggers mitochondrial uncoupling and thermogenesis. The exact role of its close homologues, UCP2 and UCP3, is unclear. Mounting evidence associates them with the control of mitochondrial superoxide production. Using CHO (Chinese-hamster ovary) cells stably expressing UCP3 or UCP1, we found no evidence for respiration uncoupling. The explanation lies in the absence of an appropriate activator of UCP protonophoric function. Accordingly, the addition of retinoic acid uncouples the respiration of the UCP1-expressing clone, but not that of the UCP3-expressing ones. In a glucose-containing medium, the extent of the hyperpolarization of mitochondria by oligomycin was close to 22 mV in the five UCP3-expressing clones, contrasting with the variable values observed with the 15 controls. Our observations suggest that, when glycolysis and mitochondria generate ATP, and in the absence of appropriate activators of proton transport, UCPs do not transport protons (uncoupling), but rather other ions of physiological relevance that control mitochondrial activity. A model is proposed using the known passive transport of pyruvate by UCP1.
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UCP-3 has no clear uncoupling effect in CHO cells overexpressing it or in rat skeletal muscles.
“Regarding UCP-3, several groups reported that UCP-3 has no clear uncoupling effect as it does, for instance, in CHO cells overexpressing this protein [19] or in rat skeletal muscles [20].”
From Mitochondrial Uncoupling: A Key Controller of Biological Processes in Physiology and Diseases (2019) · cites this paper as [19]
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Mitochondrial Uncoupling: A Key Controller of Biological Processes in Physiology and Diseases
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“Regarding UCP-3, several groups reported that UCP-3 has no clear uncoupling effect as it does, for instance, in CHO cells overexpressing this protein [19] or in rat skeletal muscles [20].”
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- Authors
- Mozo, J., Ferry, G., Studeny, A., Pecqueur, C., Rodriguez, M., Boutin, J. A., & Bouillaud, F.
- Affiliations
- Centre National de la Recherche Scientifique (FR)
- Institut de Recherches Internationales Servier (France) (FR)
- Institut de Recherches Servier, 125 chemin de Ronde, 78290 Croissy-sur-Seine, France
- Corresponding author
- Mozo, Julien
- Pecqueur, Claire
- Venue
- Biochemical Journal
- Publisher
- Portland Press Ltd.
- Published
- 2005-12-12
- Volume
- 393
- Issue
- 1
- Pages
- 431-439
- ISSN
- 0264-6021 (ISSN-L)
- 1470-8728
- PMC
- PMC1383702
- OpenAlex
- W2018289980
- Cited by
- 52
- References
- 56
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 4 · 2022: 3 · 2021: 1 · 2020: 1 · 2019: 1 · 2018: 1 · 2016: 2 · 2015: 3 · 2013: 1 · 2012: 2
- FWCI
- 2.76
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Biochemical Journal (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › ATP Synthase and ATPases Research
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Keywords
- UCP3, UCP1, UCP2, mitochondrial uncoupling, proton transport, mitochondrial membrane potential, oligomycin, retinoic acid, glucose, mitochondrial superoxide, pyruvate transport, glycolysis, ATP production, CHO cells
- MeSH terms
- Uncoupling Protein 3, Uncoupling Protein 1, Adenosine Diphosphate, Adenosine Triphosphate, Animals, Carrier Proteins, Glucose, Cricetinae, Humans, Ion Channels, Membrane Proteins, Mitochondria, Oligomycins, Oxygen Consumption, Superoxides, Uncoupling Agents, CHO Cells, Mitochondrial Proteins
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