Uncoupling proteins 2 and 3 are highly active H + transporters and highly nucleotide sensitive when activated by coenzyme Q (ubiquinone)
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Based on the discovery of coenzyme Q (CoQ) as an obligatory cofactor for H + transport by uncoupling protein 1 (UCP1) [Echtay, K. S., Winkler, E. & Klingenberg, M. (2000) Nature (London) 408, 609–613] we show here that UCP2 and UCP3 are also highly active H + transporters and require CoQ and fatty acid for H + transport, which is inhibited by low concentrations of nucleotides. CoQ is proposed to facilitate injection of H + from fatty acid into UCP. Human UCP2 and 3 expressed in Escherichia coli inclusion bodies are solubilized, and by exchange of sarcosyl against digitonin, nucleotide binding as measured with 2′- O -[5-(dimethylamino)naphthalene-1-sulfonyl]-GTP can be restored. After reconstitution into vesicles, Cl − but no H + are transported. The addition of CoQ initiates H + transport in conjunction with fatty acids. This increase is fully sensitive to nucleotides. The rates are as high as with reconstituted UCP1 from mitochondria. Maximum activity is at a molar ratio of 1:300 of CoQ:phospholipid. In UCP2 as in UCP1, ATP is a stronger inhibitor than ADP, but in UCP3 ADP inhibits more strongly than ATP. Thus UCP2 and UCP3 are regulated differently by nucleotides, in line with their different physiological contexts. These results confirm the regulation of UCP2 and UCP3 by the same factors CoQ, fatty acids, and nucleotides as UCP1. They supersede reports that UCP2 and UCP3 may not be H + transporters.
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The mechanism of UCP activation appears to involve catalysis of hydrogen transfer from fatty acid to UCPs by coenzyme Q and coupling to fatty acids.
“The mechanism appears to involve catalysis of hydrogen transfer from fatty acid to UCPs by coenzyme Q and coupling to fatty acids (94).”
From Mitochondrial Dysfunction in Diabetes: From Molecular Mechanisms to Functional Significance and Therapeutic Opportunities (2010) · cites this paper as [94]
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- Authors
- Echtay, K. S., Winkler, E., Frischmuth, K., & Klingenberg, M.
- Affiliations
- Ludwig-Maximilians-Universität München (DE)
- ORCID
- Echtay, Karim S.
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2001-02-13
- Volume
- 98
- Issue
- 4
- Pages
- 1416-1421
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC29271
- OpenAlex
- W1986003236
- Cited by
- 313
- References
- 51
- Citations by year
- 2026: 2 · 2024: 5 · 2023: 3 · 2022: 1 · 2021: 13 · 2020: 2 · 2019: 13 · 2018: 8 · 2017: 6 · 2016: 11 · 2015: 12 · 2014: 10 · 2013: 10 · 2012: 11
- FWCI
- 11.90
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Proceedings of the National Academy of Sciences (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 › ATP Synthase and ATPases Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Coenzyme Q10 studies and effects
- Keywords
- UCP2, UCP3, UCP1, proton transport, coenzyme Q10, nucleotide regulation, fatty acid uptake, ATP inhibition, ADP inhibition, mitochondrial uncoupling, proton leak, membrane reconstitution
- MeSH terms
- Uncoupling Protein 2, Uncoupling Protein 3, Animals, Carrier Proteins, Inclusion Bodies, Coenzymes, Dose-Response Relationship, Drug, Escherichia coli, Fatty Acids, Cricetinae, Humans, Hydrogen, Ion Channels, Nucleotides, Proteins, Structure-Activity Relationship, Ubiquinone, Benzoquinones, Mitochondrial Proteins, Membrane Transport Proteins
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Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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