Choosing between glycolysis and oxidative phosphorylation: a tumor’s dilemma?
Open accessAbstract
A considerable amount of knowledge has been produced during the last five years on the bioenergetics of cancer cells, leading to a better understanding of the regulation of energy metabolism during oncogenesis, or in adverse conditions of energy substrate intermittent deprivation. The general enhancement of the glycolytic machinery in various cancer cell lines is well described and recent analyses give a better view of the changes in mitochondrial oxidative phosphorylation during oncogenesis. While some studies demonstrate a reduction of oxidative phosphorylation (OXPHOS) capacity in different types of cancer cells, other investigations revealed contradictory modifications with the upregulation of OXPHOS components and a larger dependency of cancer cells on oxidative energy substrates for anabolism and energy production. This apparent conflictual picture is explained by differences in tumor size, hypoxia, and the sequence of oncogenes activated. The role of p53, C-MYC, Oct and RAS on the control of mitochondrial respiration and glutamine utilization has been explained recently on artificial models of tumorigenesis. Likewise, the generation of induced pluripotent stem cells from oncogene activation also showed the role of C-MYC and Oct in the regulation of mitochondrial biogenesis and ROS generation. In this review article we put emphasis on the description of various bioenergetic types of tumors, from exclusively glycolytic to mainly OXPHOS, and the modulation of both the metabolic apparatus and the modalities of energy substrate utilization according to tumor stage, serial oncogene activation and associated or not fluctuating microenvironmental substrate conditions. We conclude on the importance of a dynamic view of tumor bioenergetics.
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Earlier work that blocked glycolysis or oxidative phosphorylation found increased activity of the other pathway.
“These findings confirm previous studies that analyzed inhibition of either glycolysis or OXPHOS, and observed an increase in the activity of the other pathway (Hao et al., 2010; Jose et al., 2011; Birsoy et al., 2014; Dykens et al., 2008).”
From Combination of Hypoglycemia and Metformin Impairs Tumor Metabolic Plasticity and Growth by Modulating the PP2A-GSK3β-MCL-1 Axis (2019) · cites this paper as Jose et al., 2011
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- Authors
- Jose, C., Bellance, N., & Rossignol, R.
- Affiliations
- Maladies Rares: Génétique et Métabolisme (FR)
- Corresponding author
- Rossignol, Rodrigue
- ORCID
- Rossignol, Rodrigue
- Venue
- Biochimica et Biophysica Acta (BBA) - Bioenergetics
- Publisher
- Elsevier BV
- Published
- 2011-06
- Volume
- 1807
- Issue
- 6
- Pages
- 552-561
- ISSN
- 0005-2728 (ISSN-L)
- OpenAlex
- W2029436635
- Cited by
- 518
- References
- 117
- Citations by year
- 2026: 16 · 2025: 23 · 2024: 34 · 2023: 31 · 2022: 48 · 2021: 45 · 2020: 52 · 2019: 45 · 2018: 39 · 2017: 25 · 2016: 36 · 2015: 33 · 2014: 28 · 2013: 20 · 2012: 37
- FWCI
- 1.65
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Biochimica et Biophysica Acta (BBA) - Bioenergetics (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Fonds Québécois de la Recherche sur la Nature et les Technologies
- Institut National de la Santé et de la Recherche Médicale
- Cancéropôle Grand Ouest
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cancer and biochemical research
- Keywords
- tumor bioenergetics, aerobic glycolysis, oxidative phosphorylation, mitochondrial respiration, cancer cell energy metabolism, oncogene activation, hypoxia, p53, c-Myc, Oct4, Ras, glutamine utilization, mitochondrial biogenesis, reactive oxygen species, induced pluripotent stem cells, Warburg effect, metabolic therapy, tumor microenvironment
- MeSH terms
- Animals, Energy Metabolism, Glycolysis, Humans, Mitochondria, Models, Biological, Neoplasms, Oxidative Phosphorylation, Cell Respiration, Metabolic Networks and Pathways
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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