{
  "abstract": "Respiratory complex I, a crucial metabolic enzyme, uses the reducing potential of NADH to pump protons across energy-transducing membranes, but its mechanism of catalysis remains unknown. Here, guided by detailed structural information, we combine targeted mutagenesis and biophysical analyses to define the proton-pumping pathways in the three antiporter-like (proton-pumping) subunits of complex I from Paracoccus denitrificans and Escherichia coli. In Pd-CI, a four-proton pump, one of the three proton-uptake pathways is inactive, reconciling the four-proton/three-subunit mismatch. In Ec-CI two pathways are inactive - and Ec-CI pumps only two protons. We define the structural determinants for redox-coupled proton uptake, establish a mechanistic framework for proton pumping, and reveal how the proton-pumping stoichiometry has been adapted to deliver efficient energy conservation in diverse bioenergetic environments.",
  "abstract_shown": true,
  "affiliations": [
    "University of Cambridge"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 6,
  "authors": [
    {
      "name": "R. A. Waddell"
    },
    {
      "name": "H. L. Messent"
    },
    {
      "name": "M. M. Costa-Lima"
    },
    {
      "name": "J. J. Wright"
    },
    {
      "name": "J. H. Salisbury"
    },
    {
      "affs": [
        0
      ],
      "name": "J. Hirst"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/2jre822ns6z93.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.10.08.757549",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.10.08.757549v1.full",
  "id": "2jre822ns6z93",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.10.08.757549v1",
  "language": null,
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "biochemistry"
    ],
    [
      "openalex",
      "2505|Enzyme Structure and Function"
    ]
  ],
  "openalex": "W7221067877",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.10.08.757549v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-08",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/2jre822ns6z93.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:26:50Z",
      "native_id": "10.64898/2026.10.08.757549",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.10.08.757549v1"
    }
  ],
  "subjects": [
    {
      "field": "chemistry",
      "origin": "openalex:2505|Enzyme Structure and Function",
      "subfield": "materials-polymers"
    }
  ],
  "title": "A modular mechanism determines the proton-pumping stoichiometry of respiratory complex I",
  "title_text": "A modular mechanism determines the proton-pumping stoichiometry of respiratory complex I",
  "type": "preprint",
  "updated_at": "2026-10-30T12:26:50Z",
  "url": "https://research.draconitic.com/paper/2jre822ns6z93",
  "venue": "bioRxiv",
  "versions": []
}