ArticleScience advances2023
Investigation of hydrated channels and proton pathways in a high-resolution cryo-EM structure of mammalian complex I.
Article in Science advances, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 43 citations in OpenAlex.
- Review
- Hydration-Controlled Proton Transport in Respiratory Complex I.Journal of the American Chemical Society · 2026Article
- Post-catalysis structures of mitochondrial complex I with ubiquinol-10 bound in the active site.Nature communications · 2026Article
- Molecular Mechanism of Mitochondrial Complex I Disruption by m.14484T>C Underlying Leber Hereditary Optic Neuropathy.bioRxiv : the preprint server for biology · 2026Article
- Leveraging Consensus Docking Approaches for Human Mitochondrial Complexes I and III.Chemical research in toxicology · 2026Article
- Structural basis for late maturation steps of mitochondrial respiratory chain complex IV within the human respirasome.Nature communications · 2026Article
- The Protonic Brain: Nanoscale pH Dynamics, Proton Wires, and Acid-Base Information Coding in Neural Tissue.International journal of molecular sciences · 2026Review
- Proton Transfer through a Charged Conduit in Respiratory Complex I: Long-Range Effects and Conformational Gating.Journal of chemical information and modeling · 2025Article
- A fixed mutation in the respiratory complex I impairs mitochondrial bioenergetics in the endangered Apennine brown bear.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Global conformations ofScience advances · 2025Article
- A large-scale curated and filterable dataset for cryo-EM foundation model pre-training.Scientific data · 2025Article
- Exploring the Phenotypic Heterogeneity and Bioenergetic Profile of the m.13513G>A mtDNA Substitution: A Heteroplasmy Perspective.International journal of molecular sciences · 2025Article
- Kingdom-specific lipid unsaturation calibrates sequence evolution in membrane arm subunits of eukaryotic respiratory complexes.Nature communications · 2025Article
- Formation of ICell metabolism · 2025Article
- Reactive Oxygen Species in Asthma: Regulators of Macrophage Polarization and Therapeutic Implications: A Narrative Review.Journal of asthma and allergy · 2025Review
- Searching for proton transfer channels in respiratory complex I.Biophysical journal · 2024Article
- Proton-Translocating NADH-Ubiquinone Oxidoreductase: Interaction with Artificial Electron Acceptors, Inhibitors, and Potential Medicines.International journal of molecular sciences · 2024Review
- Quinone chemistry in respiratory complex I involves protonation of a conserved aspartic acid residue.FEBS letters · 2024Article
- Structure of the turnover-ready state of an ancestral respiratory complex I.Nature communications · 2024Article
- Plant supercomplex I + III2 structure and function: implications for the growing field.Biochemical Society transactions · 2024Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Respiratory complex I, a key enzyme in mammalian metabolism, captures the energy released by reduction of ubiquinone by NADH to drive protons across the inner mitochondrial membrane, generating the proton-motive force for ATP synthesis. Despite remarkable advances in structural knowledge of this complicated membrane-bound enzyme, its mechanism of catalysis remains controversial. In particular, how ubiquinone reduction is coupled to proton pumping and the pathways and mechanisms of proton translocation are contested. We present a 2.4-Å resolution cryo-EM structure of complex I from mouse heart mitochondria in the closed, active (ready-to-go) resting state, with 2945 water molecules modeled. By analyzing the networks of charged and polar residues and water molecules present, we evaluate candidate pathways for proton transfer through the enzyme, for the chemical protons for ubiquinone reduction, and for the protons transported across the membrane. Last, we compare our data to the predictions of extant mechanistic models, and identify key questions to answer in future work to test them.
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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 OpenQuestion graph.