{
  "abstract": "Hypoxia-inducible factors (HIFs) are constitutively active in clear cell renal cell carcinoma (ccRCC) cells. Here, we investigated whether these cells could still respond to hypoxia independently of canonical HIF activation. We found that hypoxia provokes a NADH reductive stress that attenuates lactate release when the supply of extracellular pyruvate becomes limited, a response that was restored by the ectopic expression of the cytosolic and mitochondria-targeted NADH oxidase (LbNOX). Suppression of the mitochondrial electron transport chain (mtETC) alone is sufficient to attenuate glycolytic flux when extracellular pyruvate is limited, a situation consistent with metabolomic data from human ccRCCs. Furthermore, this response can be mimicked by pharmacological or genetic inhibition of mitochondrial complex IV (CIV) activity and restored by the mitochondrial-targeted alternative oxidase (AOX). Therefore, our data suggest that cells can respond to low oxygen tension through a mitochondrial-dependent elevation of NADH/NAD⁺, resulting in the suppression of glycolysis when pyruvate availability is compromised.",
  "abstract_shown": true,
  "affiliations": [
    "Research Unit, Hospital of Santa Cristina, Research Institute La Princesa (IIS Princesa), Hospital de la Princesa, Universidad Autónoma de Madrid, 28009 Madrid, Spain.",
    "Laboratory of Exercise and Health, Department of Health Sciences and Technology, Swiss Federal Institute of Technology (ETH), 8603 Zurich, Switzerland.",
    "Laboratory for Orthopaedic Biomechanics, Department of Health Sciences and Technology, Swiss Federal Institute of Technology (ETH), 8008 Zurich, Switzerland.",
    "University Hospital Balgrist, University of Zurich, 8008 Zurich, Switzerland.",
    "Immunology Department, Hospital de la Princesa, Instituto Investigación Sanitaria Princesa (IIS Princesa), 28006 Madrid, Spain.",
    "CIBER de Enfermedades Respiratorias (CIBERES), Carlos III Health Institute, 28029 Madrid, Spain.",
    "CIBER de Enfermedades Cardiovasculares (CIBERCV), Carlos III Health Institute, 28029 Madrid, Spain.",
    "Unidad de Videomicroscopia, Instituto Investigación Sanitaria Princesa (IIS-IP), 28006 Madrid, Spain.",
    "Centro Nacional de Investigaciónes Cardiovasculares (CNIC) Carlos III, 28029 Madrid, Spain."
  ],
  "article_type": "Research Article",
  "arxiv": null,
  "author_total": 13,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Andrea Guajardo-Grence",
      "orcid": "0000-0002-4437-8529"
    },
    {
      "affs": [
        0
      ],
      "name": "María Fernández-Lamadrid"
    },
    {
      "affs": [
        1,
        2,
        3
      ],
      "name": "Greta Moschini",
      "orcid": "0000-0002-9845-9965"
    },
    {
      "affs": [
        4
      ],
      "name": "Lidia Marin-Algeciras",
      "orcid": "0009-0008-4749-3048"
    },
    {
      "affs": [
        0
      ],
      "name": "Claudia Mesa-Ciller",
      "orcid": "0000-0001-9807-5550"
    },
    {
      "affs": [
        4
      ],
      "name": "Rosa Andreu Martínez",
      "orcid": "0000-0002-2553-7344"
    },
    {
      "affs": [
        0
      ],
      "name": "Lucía Fernández-Arroyo",
      "orcid": "0000-0001-9229-8470"
    },
    {
      "affs": [
        0
      ],
      "name": "Rebeca Vázquez Muñoz",
      "orcid": "0009-0000-6454-6924"
    },
    {
      "affs": [
        4,
        5
      ],
      "name": "María José Calzada"
    },
    {
      "affs": [
        4,
        6,
        7
      ],
      "name": "Noa Beatriz Martín-Cófreces",
      "orcid": "0000-0003-0439-8979"
    },
    {
      "affs": [
        8
      ],
      "name": "José Antonio Enríquez",
      "orcid": "0000-0002-3671-2961"
    },
    {
      "affs": [
        1
      ],
      "name": "Katrien De Bock",
      "orcid": "0000-0001-8232-4663"
    },
    {
      "affs": [
        0,
        6
      ],
      "name": "Julián Aragonés",
      "orcid": "0000-0002-0193-4679"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/5qbys8g2b8vk7.bib",
  "cited_by": 0,
  "doi": "10.1126/sciadv.aed1177",
  "fulltext_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13721980/?tool=EBI",
  "id": "5qbys8g2b8vk7",
  "issns": [
    "2375-2548"
  ],
  "landing_url": "https://www.science.org/doi/abs/10.1126/sciadv.aed1177",
  "language": "eng",
  "licence": "CC-BY-NC",
  "licence_label": "CC BY-NC",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Biomedicine and Life Sciences"
    ],
    [
      "heading",
      "Cancer"
    ],
    [
      "heading",
      "Cell Biology"
    ],
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      "heading",
      "Research Article"
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      "heading",
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  "openalex": null,
  "pdf_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13721980/pdf/?tool=EBI",
  "pmcid": "PMC13721980",
  "pmid": "42962020",
  "published": "2026-10-30",
  "publisher": "American Association for the Advancement of Science (AAAS)",
  "ris": "https://research.draconitic.com/paper/5qbys8g2b8vk7.ris",
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  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "heading:Cell Biology",
      "subfield": "cell-biology"
    },
    {
      "field": "medicine",
      "origin": "heading:Cancer",
      "subfield": "oncology"
    }
  ],
  "title": "Oxygen-dependent constraint of glycolysis through the mitochondrial electron transport chain",
  "title_text": "Oxygen-dependent constraint of glycolysis through the mitochondrial electron transport chain",
  "type": "peer-reviewed",
  "updated_at": "2026-11-03T12:22:34Z",
  "url": "https://research.draconitic.com/paper/5qbys8g2b8vk7",
  "venue": "Science Advances",
  "versions": []
}