ArticleNature communications2023
Molecular determinants of inhibition of UCP1-mediated respiratory uncoupling.
Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 20 citations in OpenAlex.
- Article
- A Structural Context for the Mechanisms of Uncoupling Protein 1 in Brown Fat Thermogenesis.Acta physiologica (Oxford, England) · 2026Review
- Targeting Mitochondria in Aging-Related Diseases: Therapeutic Potential and Obstacles.MedComm · 2026Review
- Characterization of Recombinant GMPR fromBiology · 2026Article
- Assessing the interaction of the UCP system and fatty acids on epicardial adipose tissue mitochondrial respiration.European journal of clinical investigation · 2026Article
- Deciphering Uncoupling Proteins in Cellular Homeostasis and Metabolic Health.International journal of biological sciences · 2026Review
- Interactions of Arachidonic Acid with AAC1 and UCP1.International journal of molecular sciences · 2025Article
- Regulation of redox homeostasis by ATF4-MTHFD2 axis during white adipose tissue browning.Redox biology · 2025Article
- Fine-tuning the yeast GAL10 promoter and growth conditions for efficient recombinant membrane protein production and purification.Protein science : a publication of the Protein Society · 2025Article
- Proton conductance by human uncoupling protein 1 is inhibited by purine and pyrimidine nucleotides.The EMBO journal · 2025Article
- Expanded Functionality and Portability for the Colvars Library.The journal of physical chemistry. B · 2024Article
- Review
- Unravelling the Influence of Endocrine-Disrupting Chemicals on Obesity Pathophysiology Pathways.Advances in experimental medicine and biology · 2024Review
- Phylogenetic Analysis Guides Transporter Protein Deorphanization: A Case Study of the SLC25 Family of Mitochondrial Metabolite Transporters.Biomolecules · 2023Article
- Molecular determinants of inhibition of UCP1-mediated respiratory uncoupling.Nature communications · 2023Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Brown adipose tissue expresses uncoupling protein 1 (UCP1), which dissipates energy as heat, making it a target for treating metabolic disorders. Here, we investigate how purine nucleotides inhibit respiration uncoupling by UCP1. Our molecular simulations predict that GDP and GTP bind UCP1 in the common substrate binding site in an upright orientation, where the base moiety interacts with conserved residues R92 and E191. We identify a triplet of uncharged residues, F88/I187/W281, forming hydrophobic contacts with nucleotides. In yeast spheroplast respiration assays, both I187A and W281A mutants increase the fatty acid-induced uncoupling activity of UCP1 and partially suppress the inhibition of UCP1 activity by nucleotides. The F88A/I187A/W281A triple mutant is overactivated by fatty acids even at high concentrations of purine nucleotides. In simulations, E191 and W281 interact with purine but not pyrimidine bases. These results provide a molecular understanding of the selective inhibition of UCP1 by purine nucleotides.
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