ArticleCellular and molecular life sciences : CMLS2014
Single-nucleotide evolution quantifies the importance of each site along the structure of mitochondrial carriers.
Article in Cellular and molecular life sciences : CMLS, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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37 citing papers in PubMed, 63 citations in OpenAlex.
- Evolutionary history and recombination in the mitochondrial carrier SLC25 superfamily analyzed by similarities in the exon and transmembrane α-helix sequences.Protein science : a publication of the Protein Society · 2026Article
- From the cytosol to the inner membrane: biogenesis of the mitochondrial carrier family.Protein science : a publication of the Protein Society · 2026Review
- SLC25A mitochondrial carriers as biomarkers and therapeutic targets of spaceflight-induced dysfunction: the ADP/ATP carrier (AAC3) as a structural case study.Journal of translational medicine · 2025Article
- Targeting mitochondrial transporters and metabolic reprogramming for disease treatment.Journal of translational medicine · 2025Review
- Discovery of therapeutic AGC2 modulators by combining docking, binding, and vesicle-based transport assays.Journal of translational medicine · 2025Article
- Carnitine O-Acetyltransferase as a Central Player in Lipid and Branched-Chain Amino Acid Metabolism, Epigenetics, Cell Plasticity, and Organelle Function.Biomolecules · 2025Review
- Developmental and Epileptic Encephalopathy: Pathogenesis of Intellectual Disability Beyond Channelopathies.Biomolecules · 2025Review
- Modulatory Effect of Nicotinamide Adenine Dinucleotide Phosphate (NADPH) on the 2-Oxoglutarate Mitochondrial Carrier.Molecules (Basel, Switzerland) · 2024Article
- Insights into Transient Dimerisation of Carnitine/Acylcarnitine Carrier (SLC25A20) from Sarkosyl/PAGE, Cross-Linking Reagents, and Comparative Modelling Analysis.Biomolecules · 2024Article
- Layered mechanisms regulating the human mitochondrial NAD+ transporter SLC25A51.Biochemical Society transactions · 2023Review
- Dynamics of SLC25A51 reveal preference for oxidized NADEMBO reports · 2023Article
- Membrane Transporters Involved in Iron Trafficking: Physiological and Pathological Aspects.Biomolecules · 2023Review
- In Silico Analysis of the Structural Dynamics and Substrate Recognition Determinants of the Human Mitochondrial Carnitine/Acylcarnitine SLC25A20 Transporter.International journal of molecular sciences · 2023Article
- The Mycotoxin Patulin Inhibits the Mitochondrial Carnitine/Acylcarnitine Carrier (SLC25A20) by Interaction with Cys136 Implications for Human Health.International journal of molecular sciences · 2023Article
- New Insights Regarding Hemin Inhibition of the Purified Rat Brain 2-Oxoglutarate Carrier and Relationships with Mitochondrial Dysfunction.Journal of clinical medicine · 2022Article
- Function-Related Asymmetry of the Interactions between Matrix Loops and Conserved Sequence Motifs in the Mitochondrial ADP/ATP Carrier.International journal of molecular sciences · 2022Article
- Citrate Regulates theJournal of fungi (Basel, Switzerland) · 2022Article
- The effects of cardiolipin on the structural dynamics of the mitochondrial ADP/ATP carrier in its cytosol-open state.Journal of lipid research · 2022Article
- Personalized Medicine in Mitochondrial Health and Disease: Molecular Basis of Therapeutic Approaches Based on Nutritional Supplements and Their Analogs.Molecules (Basel, Switzerland) · 2022Review
- Investigating the Broad Matrix-Gate Network in the Mitochondrial ADP/ATP Carrier through Molecular Dynamics Simulations.Molecules (Basel, Switzerland) · 2022Article
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Authors and funding
3 authors at 1 institution in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mitochondrial carriers are membrane-embedded proteins consisting of a tripartite structure, a three-fold pseudo-symmetry, related sequences, and similar folding whose main function is to catalyze the transport of various metabolites, nucleotides, and coenzymes across the inner mitochondrial membrane. In this study, the evolutionary rate in vertebrates was screened at each of the approximately 50,000 nucleotides corresponding to the amino acids of the 53 human mitochondrial carriers. Using this information as a starting point, a scoring system was developed to quantify the evolutionary pressure acting on each site of the common mitochondrial carrier structure and estimate its functional or structural relevance. The degree of evolutionary selection varied greatly among all sites, but it was highly similar among the three symmetric positions in the tripartite structure, known as symmetry-related sites or triplets, suggesting that each triplet constitutes an evolutionary unit. Based on evolutionary selection, 111 structural sites (37 triplets) were found to be important. These sites play a key role in structure/function of mitochondrial carriers and are involved in either conformational changes (sites of the gates, proline-glycine levels, and aromatic belts) or in binding and specificity of the transported substrates (sites of the substrate-binding area in between the two gates). Furthermore, the evolutionary pressure analysis revealed that the matrix short helix sites underwent different degrees of selection with high inter-paralog variability. Evidence is presented that these sites form a new sequence motif in a subset of mitochondrial carriers, including the ADP/ATP translocator, and play a regulatory function by interacting with ligands and/or proteins of the mitochondrial matrix.
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