Cited by 1,650Cancer, Hypoxia, and MetabolismCancer-related Molecular PathwaysMetabolism, Diabetes, and Cancer

p53 Regulates Mitochondrial Respiration

Matoba, Satoaki, Kang, Ju-Gyeong, Patino, Willmar D., Wragg, Andrew, Boehm, Manfred, Gavrilova, Oksana, Hurley, Paula J., Bunz, Fred +1 more·2006·Science

Abstract

The energy that sustains cancer cells is derived preferentially from glycolysis. This metabolic change, the Warburg effect, was one of the first alterations in cancer cells recognized as conferring a survival advantage. Here, we show that p53, one of the most frequently mutated genes in cancers, modulates the balance between the utilization of respiratory and glycolytic pathways. We identify Synthesis of Cytochrome c Oxidase 2 (SCO2) as the downstream mediator of this effect in mice and human cancer cell lines. SCO2 is critical for regulating the cytochrome c oxidase (COX) complex, the major site of oxygen utilization in the eukaryotic cell. Disruption of the SCO2 gene in human cancer cells with wild-type p53 recapitulated the metabolic switch toward glycolysis that is exhibited by p53-deficient cells. That SCO2 couples p53 to mitochondrial respiration provides a possible explanation for the Warburg effect and offers new clues as to how p53 might affect aging and metabolism.

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Crossref · 10.1126/science.1126863

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  • p53 regulates transcription of TIGAR and SCO2, which have key roles in glucose utilization and mitochondrial respiration.

    “This link has been strengthened by recent reports that p53 regulates the transcription of two proteins, TP53-induced glycolosis and apoptosis regulator (TIGAR) and the SCO cytochrome oxidase deficient homologue 2 (SCO2), which have key roles in the utilization of glucose and mitochondrial respiration, respectively 83, 84 .”

    From The common biology of cancer and ageing (2007) · cites this paper as [84]

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Authors
Matoba, S., Kang, J.-G., Patino, W. D., Wragg, A., Boehm, M., Gavrilova, O., Hurley, P. J., Bunz, F., & Hwang, P. M.
Affiliations
National Institutes of Health (US)
Corresponding author
Hwang, Paul M.
Venue
Science
Published
2006-06-16
Volume
312
Issue
5780
Pages
1650-1653
ISSN
  • 0036-8075 (ISSN-L)
  • 1095-9203
OpenAlex
W2062515127
Cited by
1,650
References
31
Citations by year
2026: 25 · 2025: 28 · 2024: 41 · 2023: 44 · 2022: 60 · 2021: 73 · 2020: 91 · 2019: 61 · 2018: 81 · 2017: 72 · 2016: 80 · 2015: 95 · 2014: 122 · 2013: 123 · 2012: 129
FWCI
38.39
Type
journal article
Language
en
Open access
closed
Locations
  • Science (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Institutes of Health
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
  • Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
Keywords
p53, mitochondrial respiration, Warburg effect, glycolysis, SCO2, cytochrome c oxidase, cancer metabolism, tumor energy metabolism, p53-deficient cells, aging
MeSH terms
Adenosine Triphosphate, Animals, Carrier Proteins, Cell Survival, Electron Transport Complex IV, Glycolysis, Humans, Membrane Proteins, Mice, Inbred C57BL, Mitochondria, Mitochondria, Liver, Mutation, Oxygen Consumption, Proteins, Recombination, Genetic, Transcription, Genetic, Transcriptional Activation, Gene Expression Regulation, Neoplastic, Genes, p53, Tumor Suppressor Protein p53, Molecular Chaperones, Cell Respiration, Mitochondrial Proteins, RNA, Small Interfering, Cell Line, Tumor, Mice

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