ArticleBiomolecules2021
Mitochondrial Uncoupling Proteins (UCP1-UCP3) and Adenine Nucleotide Translocase (ANT1) Enhance the Protonophoric Action of 2,4-Dinitrophenol in Mitochondria and Planar Bilayer Membranes.
Article in Biomolecules, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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14 citing papers in PubMed, 31 citations in OpenAlex.
- Molecular mechanisms of mitochondrial uncoupling: focus on 2,4-dinitrophenol.European biophysics journal : EBJ · 2026Review
- Interactions of Arachidonic Acid with AAC1 and UCP1.International journal of molecular sciences · 2025Article
- Mitochondrial membrane potential and compartmentalized signaling: Calcium, ROS, and beyond.Redox biology · 2025Review
- Molecular Dynamics Simulations of a Putative Novel Mechanism for UCP1-Assisted FA Anion Transport.Acta physiologica (Oxford, England) · 2025Article
- Exploring the proton transport mechanism of the mitochondrial ADP/ATP carrier: FA-cycling hypothesis and beyond.Protein science : a publication of the Protein Society · 2025Review
- Theoretical and Experimental Study of the Interaction of Protonophore Uncouplers and Decoupling Agents with Functionally Active Mitochondria.Cell biochemistry and biophysics · 2024Article
- The 2-oxoglutarate/malate carrier extends the family of mitochondrial carriers capable of fatty acid and 2,4-dinitrophenol-activated proton transport.Acta physiologica (Oxford, England) · 2024Article
- Mitochondrial network adaptations of microglia reveal sex-specific stress response after injury and UCP2 knockout.iScience · 2023Article
- Informing the Cannabis Conjecture: From Life's Beginnings to Mitochondria, Membranes and the Electrome-A Review.International journal of molecular sciences · 2023Review
- Article
- Mitochondrial ATP Synthase and Mild Uncoupling by Butyl Ester of Rhodamine 19, C4R1.Antioxidants (Basel, Switzerland) · 2023Article
- 3,5-T2-an Endogenous Thyroid Hormone Metabolite as Promising Lead Substance in Anti-Steatotic Drug Development?Metabolites · 2022Review
- Pioglitazone Is a Mild Carrier-Dependent Uncoupler of Oxidative Phosphorylation and a Modulator of Mitochondrial Permeability Transition.Pharmaceuticals (Basel, Switzerland) · 2021Article
- Fifty Years of Research on Protonophores: Mitochondrial Uncoupling As a Basis for Therapeutic Action.Acta naturaeArticle
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Authors and funding
10 authors at 4 institutions in 4 countries.
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Abstract
2,4-Dinitrophenol (DNP) is a classic uncoupler of oxidative phosphorylation in mitochondria which is still used in "diet pills", despite its high toxicity and lack of antidotes. DNP increases the proton current through pure lipid membranes, similar to other chemical uncouplers. However, the molecular mechanism of its action in the mitochondria is far from being understood. The sensitivity of DNP's uncoupling action in mitochondria to carboxyatractyloside, a specific inhibitor of adenine nucleotide translocase (ANT), suggests the involvement of ANT and probably other mitochondrial proton-transporting proteins in the DNP's protonophoric activity. To test this hypothesis, we investigated the contribution of recombinant ANT1 and the uncoupling proteins UCP1-UCP3 to DNP-mediated proton leakage using the well-defined model of planar bilayer lipid membranes. All four proteins significantly enhanced the protonophoric effect of DNP. Notably, only long-chain free fatty acids were previously shown to be co-factors of UCPs and ANT1. Using site-directed mutagenesis and molecular dynamics simulations, we showed that arginine 79 of ANT1 is crucial for the DNP-mediated increase of membrane conductance, implying that this amino acid participates in DNP binding to ANT1.
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