ArticleProceedings of the National Academy of Sciences of the United States of America2015
Uncoupling protein 1 binds one nucleotide per monomer and is stabilized by tightly bound cardiolipin.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers.
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Who cites it
60 citing papers in PubMed, 96 citations in OpenAlex.
- RUNX2 inhibitor CADD522 improves bone microarchitecture and lipid metabolism in post-menopausal bone loss.npj drug discovery · 2026Article
- ANXA1 improves mitochondrial homeostasis through uncoupling protein 1 in diabetic nephropathy.Journal of advanced research · 2026Article
- UCP1-Dependent Thermogenic Adipose Tissue in Human Disease: Adipose-Centered Mechanisms, Biomarker Limitations, and Translational Perspectives.International journal of molecular sciences · 2026Review
- Article
- A Structural Context for the Mechanisms of Uncoupling Protein 1 in Brown Fat Thermogenesis.Acta physiologica (Oxford, England) · 2026Review
- Characterization of Recombinant GMPR fromBiology · 2026Article
- Emerging complexities of phospholipid metabolism in adipose tissue.Molecules and cells · 2026Review
- Palmitic acid induces UCP1-independent mitochondrial depolarization specifically in brown adipose tissue.The Journal of biological chemistry · 2026Article
- Interactions of Arachidonic Acid with AAC1 and UCP1.International journal of molecular sciences · 2025Article
- The peculiar properties of mitochondrial carriers of the SLC25 family.The Biochemical journal · 2025Review
- The Role of Cardiolipin in Brain Bioenergetics, Neuroinflammation, and Neurodegeneration.Molecular neurobiology · 2025Review
- Proton conductance by human uncoupling protein 1 is inhibited by purine and pyrimidine nucleotides.The EMBO journal · 2025Article
- Interconnected roles of mitochondrial carrier proteins ANT, PFrontiers in molecular biosciences · 2025Article
- Annonaceous acetogenins mimic AA005 targets mitochondrial trifunctional enzyme alpha subunit to treat obesity in male mice.Nature communications · 2024Article
- Insights into Transient Dimerisation of Carnitine/Acylcarnitine Carrier (SLC25A20) from Sarkosyl/PAGE, Cross-Linking Reagents, and Comparative Modelling Analysis.Biomolecules · 2024Article
- Mitochondrial membrane lipids in the regulation of bioenergetic flux.Cell metabolism · 2024Review
- Human mitochondrial carriers of the SLC25 family function as monomers exchanging substrates with a ping-pong kinetic mechanism.The EMBO journal · 2024Article
- Layered mechanisms regulating the human mitochondrial NAD+ transporter SLC25A51.Biochemical Society transactions · 2023Review
- Article
- Structural basis of purine nucleotide inhibition of human uncoupling protein 1.Science advances · 2023Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Uncoupling protein 1 (UCP1) catalyzes fatty acid-activated, purine nucleotide-sensitive proton leak across the mitochondrial inner membrane of brown adipose tissue to produce heat, and could help combat obesity and metabolic disease in humans. Studies over the last 30 years conclude that the protein is a dimer, binding one nucleotide molecule per two proteins, and unlike the related mitochondrial ADP/ATP carrier, does not bind cardiolipin. Here, we have developed novel methods to purify milligram amounts of UCP1 from native sources by using covalent chromatography that, unlike past methods, allows the protein to be prepared in defined conditions, free of excess detergent and lipid. Assessment of purified preparations by TLC reveal that UCP1 retains tightly bound cardiolipin, with a lipid phosphorus content equating to three molecules per protein, like the ADP/ATP carrier. Cardiolipin stabilizes UCP1, as demonstrated by reconstitution experiments and thermostability assays, indicating that the lipid has an integral role in the functioning of the protein, similar to other mitochondrial carriers. Furthermore, we find that UCP1 is not dimeric but monomeric, as indicated by size exclusion analysis, and has a ligand titration profile in isothermal calorimetric measurements that clearly shows that one nucleotide binds per monomer. These findings reveal the fundamental composition of UCP1, which is essential for understanding the mechanism of the protein. Our assessment of the properties of UCP1 indicate that it is not unique among mitochondrial carriers and so is likely to use a common exchange mechanism in its primary function in brown adipose tissue mitochondria.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.