Skip to content
DraconiticResearch
Search Sources API
203,203 studies31 sourcesUpdated 19 min ago
Peer-reviewedCC BY 4.0eLife

Cancer cells differentially modulate mitochondrial respiration to alter redox state and enable biomass synthesis in nutrient-limited environments

  • Sarah M Chang1,2,3
  • Muhammad Bin Munim1,2
  • Sonia E Trojan1,4
  • Huel Cox III1,3
  • Anna Shevzov-Zebrun1,2
  • Keene L Abbott1,2
  • Renee Chang1,2
  • Matthew G Vander Heiden1,2,5
5 affiliations
  1. 1Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, United States
  2. 2Department of Biology, Massachusetts Institute of Technology, Cambridge, United States
  3. 3Harvard/MIT MD-PhD Program, Boston, United States
  4. 4Jagiellonian University Medical College, Faculty of Medicine, Chair of Medical Biochemistry, Krakow, Poland
  5. 5Dana-Farber Cancer Institute, Boston, United States
Read full textPDFDOICite

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.

Related

  1. Integrated toxicogenomic and single-nucleus transcriptomic analyses prioritize SDHB and NDUFAB1 in mitochondrial respiration-associated remodeling during cisplatin-induced acute kidney injury
    Dianjie Zeng, Yunhui He, Huijie Hu +2
    Frontiers in cell and developmental biologyPeer-reviewedCC BYFull textGeneral biochemistryEurope PMC
  2. Mitochondrial ribosome content as a proxy for respiration
    Francis Mairet
    Biology LettersPeer-reviewedCC BYMolecular biology & gene regulationHAL
  3. Peptidomimetics Inspired by α-Synuclein or Its Chaperone αB-Crystallin Differentially Modulate α-Synuclein Aggregation
    Nicolo Bisi, Josine Kothuis, Julia Kaffy +14
    Journal of Medicinal ChemistryPeer-reviewedCC BY 4.0Full text1 citedBiophysicsStructural biologyHAL
  4. Oliceridine and morphine differentially modulate the gut microbiota-intestinal barrier axis in a rat postoperative pain model.
    Keying Li, Sufang Jiang, Peiying Huang +5
    Frontiers in pharmacologyPeer-reviewedCC BYFull textMolecular biology & gene regulationEurope PMCCrossref
  5. Protein-rich food matrices from alternative and conventional sources differentially shape gut microbiota, metabolic function, and muscle protein synthesis
    Mariana Villegas-Romero, Mónica Sánchez-Tapia, Julieta Hernández-Acosta +7
    NPJ Science of FoodPeer-reviewedCC BY-NC-ND 4.0Full textMolecular biology & gene regulationPMC

Cite

BibTeXRIS
BibTeX
@article{chang2026cancer,
  title = {{Cancer cells differentially modulate mitochondrial respiration to alter redox state and enable biomass synthesis in nutrient-limited environments}},
  author = {Sarah M Chang and Muhammad Bin Munim and Sonia E Trojan and Huel Cox III and Anna Shevzov-Zebrun and Keene L Abbott and Renee Chang and Matthew G Vander Heiden},
  journal = {eLife},
  year = {2026},
  month = nov,
  doi = {10.7554/elife.107123},
  url = {https://elifesciences.org/articles/107123},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Cancer cells differentially modulate mitochondrial respiration to alter redox state and enable biomass synthesis in nutrient-limited environments
AU  - Sarah M Chang
AU  - Muhammad Bin Munim
AU  - Sonia E Trojan
AU  - Huel Cox III
AU  - Anna Shevzov-Zebrun
AU  - Keene L Abbott
AU  - Renee Chang
AU  - Matthew G Vander Heiden
PY  - 2026
DA  - 2026/11/04
JO  - eLife
DO  - 10.7554/elife.107123
UR  - https://elifesciences.org/articles/107123
AB  - 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.
SN  - 2050-084X
ER  -