ArticleInternational journal of molecular sciences2023
FA Sliding as the Mechanism for the ANT1-Mediated Fatty Acid Anion Transport in Lipid Bilayers.
Article in International journal of molecular sciences, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 21 citations in OpenAlex.
- Molecular mechanisms of mitochondrial uncoupling: focus on 2,4-dinitrophenol.European biophysics journal : EBJ · 2026Review
- Fatty acids promote uncoupled respiration via ATP/ADP carriers in white adipocytes.Nature metabolism · 2026Article
- Unveiling Specificity, Redundancy, and Promiscuity of FiveInternational journal of molecular sciences · 2026Article
- Interactions of Arachidonic Acid with AAC1 and UCP1.International journal of molecular sciences · 2025Article
- 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
- Modeling the different conformations of the human mitochondrial ADP/ATP carrier using AlphaFold and molecular dynamics simulations of the protein-ligand complexes.Computational and structural biotechnology journal · 2025Article
- Interconnected roles of mitochondrial carrier proteins ANT, PFrontiers in molecular biosciences · 2025Article
- MCNN_MC: Computational Prediction of Mitochondrial Carriers and Investigation of Bongkrekic Acid Toxicity Using Protein Language Models and Convolutional Neural Networks.Journal of chemical information and modeling · 2024Article
- ANT-Mediated Inhibition of the Permeability Transition Pore Alleviates Palmitate-Induced Mitochondrial Dysfunction and Lipotoxicity.Biomolecules · 2024Article
- Dual-Probe Activity-Based Protein Profiling Reveals Site-Specific Differences in Protein Binding of EGFR-Directed Drugs.ACS chemical biology · 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
- Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 3 countries.
Funding
Abstract
Mitochondrial adenine nucleotide translocase (ANT) exchanges ADP for ATP to maintain energy production in the cell. Its protonophoric function in the presence of long-chain fatty acids (FA) is also recognized. Our previous results imply that proton/FA transport can be best described with the FA cycling model, in which protonated FA transports the proton to the mitochondrial matrix. The mechanism by which ANT1 transports FA anions back to the intermembrane space remains unclear. Using a combined approach involving measurements of the current through the planar lipid bilayers reconstituted with ANT1, site-directed mutagenesis and molecular dynamics simulations, we show that the FA anion is first attracted by positively charged arginines or lysines on the matrix side of ANT1 before moving along the positively charged protein-lipid interface and binding to R79, where it is protonated. We show that R79 is also critical for the competitive binding of ANT1 substrates (ADP and ATP) and inhibitors (carboxyatractyloside and bongkrekic acid). The binding sites are well conserved in mitochondrial SLC25 members, suggesting a general mechanism for transporting FA anions across the inner mitochondrial membrane.
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Registered trials
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 Socratic graph.