{
  "abstract": "The cell NAD+/NADH ratio can constrain biomass synthesis and influence proliferation in nutrient-limited environments. However, which cell processes regulate the NAD+/NADH ratio is not known. Here, we find that some cancer cells elevate the NAD+/NADH ratio in response to serine deprivation by increasing mitochondrial respiration. Cancer cells that elevate mitochondrial respiration have higher serine production and proliferation in serine-limiting conditions than cells with no mitochondrial respiration response, independent of serine synthesis enzyme expression. Increases in mitochondrial respiration and the NAD+/NADH ratio promote serine synthesis regardless of whether serine is environmentally limiting. Lipid deprivation can increase the NAD+/NADH ratio via mitochondrial respiration in some cells, including cells that do not increase respiration following serine deprivation. Thus, in cancer cells where lipid depletion raises the NAD+/NADH ratio, proliferation in serine-depleted environments improves when lipids are also depleted. Taken together, these data suggest that changes in mitochondrial respiration in response to nutrient deprivation can influence the NAD+/NADH ratio in a cell-specific manner to impact oxidative biomass synthesis and proliferation. Given the complexity of tumor microenvironments, this work provides a metabolic framework for understanding how levels of more than one environmental nutrient affect cancer cell proliferation.",
  "abstract_shown": true,
  "affiliations": [
    "Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, United States",
    "Department of Biology, Massachusetts Institute of Technology, Cambridge, United States",
    "Harvard/MIT MD-PhD Program, Boston, United States",
    "Jagiellonian University Medical College, Faculty of Medicine, Chair of Medical Biochemistry, Krakow, Poland",
    "Dana-Farber Cancer Institute, Boston, United States"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 8,
  "authors": [
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Sarah M Chang",
      "orcid": "0000-0002-0036-1071"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Muhammad Bin Munim"
    },
    {
      "affs": [
        0,
        3
      ],
      "name": "Sonia E Trojan"
    },
    {
      "affs": [
        0,
        2
      ],
      "name": "Huel Cox III",
      "orcid": "0009-0004-5808-868X"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Anna Shevzov-Zebrun"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Keene L Abbott",
      "orcid": "0000-0002-6166-704X"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Renee Chang"
    },
    {
      "affs": [
        0,
        1,
        4
      ],
      "name": "Matthew G Vander Heiden",
      "orcid": "0000-0002-6702-4192"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/3v1fptj7vz6ma.bib",
  "cited_by": 2,
  "doi": "10.7554/elife.107123",
  "fulltext_url": "https://elifesciences.org/articles/107123",
  "id": "3v1fptj7vz6ma",
  "issns": [
    "2050-084X"
  ],
  "landing_url": "https://elifesciences.org/articles/107123",
  "language": "en",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "elife",
      "biochemistry-chemical-biology"
    ],
    [
      "elife",
      "cancer-biology"
    ],
    [
      "heading",
      "Biochemistry and Chemical Biology"
    ],
    [
      "heading",
      "Cancer Biology"
    ],
    [
      "heading",
      "Research Article"
    ],
    [
      "openalex",
      "1306|Cancer, Hypoxia, and Metabolism"
    ]
  ],
  "openalex": "W4411715518",
  "pdf_url": "https://cdn.elifesciences.org/articles/107123/elife-107123-v1.pdf",
  "pmcid": "PMC13734678",
  "pmid": "42981214",
  "published": "2026-11-04",
  "publisher": "eLife Sciences Publications",
  "ris": "https://research.draconitic.com/paper/3v1fptj7vz6ma.ris",
  "sources": [
    {
      "first_seen": "2026-11-05T12:20:15Z",
      "native_id": "107123",
      "source": "elife",
      "url": "https://elifesciences.org/articles/107123"
    },
    {
      "first_seen": "2026-11-08T12:24:06Z",
      "native_id": "PMC13734678",
      "source": "pmc",
      "url": "https://doi.org/10.7554/elife.107123"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "elife:biochemistry-chemical-biology",
      "subfield": "general"
    },
    {
      "field": "medicine",
      "origin": "elife:cancer-biology",
      "subfield": "oncology"
    }
  ],
  "title": "Cancer cells differentially modulate mitochondrial respiration to alter redox state and enable biomass synthesis in nutrient-limited environments",
  "title_text": "Cancer cells differentially modulate mitochondrial respiration to alter redox state and enable biomass synthesis in nutrient-limited environments",
  "type": "peer-reviewed",
  "updated_at": "2026-11-08T12:24:06Z",
  "url": "https://research.draconitic.com/paper/3v1fptj7vz6ma",
  "venue": "eLife",
  "versions": []
}