ArticleJournal of chemical information and modeling2021
Structural Insights into the Human Mitochondrial Pyruvate Carrier Complexes.
Article in Journal of chemical information and modeling, 2021. 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, 17 citations in OpenAlex.
- Coapplication of Adenine with Inosine or Guanosine Supports Rapid ATP Restoration by ATP-deprived Cultured Primary Astrocytes.Neurochemical research · 2025Article
- Structure of human mitochondrial pyruvate carrier MPC1 and MPC2 complex.Nature communications · 2025Article
- ALDH4A1 functions as an active component of the MPC complex maintaining mitochondrial pyruvate import for TCA cycle entry and tumour suppression.Nature cell biology · 2025Article
- Article
- Computational studies on the functional and structural impact of pathogenic mutations in enzymes.Protein science : a publication of the Protein Society · 2025Review
- The Role of Mitochondrial Pyruvate Carrier in Neurological Disorders.Molecular neurobiology · 2025Review
- Advancing mitochondrial therapeutics: Synthesis and pharmacological evaluation of pyrazole-based inhibitors targeting the mitochondrial pyruvate carrier.European journal of medicinal chemistry · 2025Article
- Advances in the Development of Mitochondrial Pyruvate Carrier Inhibitors for Therapeutic Applications.Biomolecules · 2025Review
- ATP Restoration by ATP-Deprived Cultured Primary Astrocytes.Neurochemical research · 2024Article
- Computational structural prediction and chemical inhibition of the human mitochondrial pyruvate carrier protein heterodimer complex.bioRxiv : the preprint server for biology · 2024Article
- Modulation of Pyruvate Export and Extracellular Pyruvate Concentration in Primary Astrocyte Cultures.Neurochemical research · 2024Article
- Fifty years of the mitochondrial pyruvate carrier: New insights into its structure, function, and inhibition.Acta physiologica (Oxford, England) · 2023Review
- Consumption and Metabolism of Extracellular Pyruvate by Cultured Rat Brain Astrocytes.Neurochemical research · 2023Article
- Experimental Investigations on the Structure of Yeast Mitochondrial Pyruvate Carriers.Membranes · 2022Article
- Identification of Novel Mitochondrial Pyruvate Carrier Inhibitors by Homology Modeling and Pharmacophore-Based Virtual Screening.Biomedicines · 2022Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Pyruvate metabolism requires the mitochondrial pyruvate carrier (MPC) proteins to transport pyruvate from the intermembrane space through the inner mitochondrial membrane to the mitochondrial matrix. The lack of the atomic structures of MPC hampers the understanding of the functional states of MPC and molecular interactions with the substrate or inhibitor. Here, we develop the de novo models of human MPC complexes and characterize the conformational dynamics of the MPC heterodimer formed by MPC1 and MPC2 (MPC1/2) by computational simulations. Our results reveal that functional MPC1/2 prefers to adopt an inward-open conformation, with the carrier open to the matrix side, whereas the outward-open states are less populated. The energy barrier for pyruvate transport in MPC1/2 is low enough, and the inhibitor UK5099 blocks the pyruvate transport by stably binding to MPC1/2. Notably, consistent with experimental results, the MPC1 L79H mutation significantly alters the conformations of MPC1/2 and thus fails for substrate transport. However, the MPC1 R97W mutation seems to retain the transport activity. The present de novo models of MPC complexes provide structural insights into the conformational states of MPC complexes and mechanistic understanding of interactions between the substrate/inhibitor and MPC proteins.
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