A Role for the Mitochondrial Pyruvate Carrier as a Repressor of the Warburg Effect and Colon Cancer Cell Growth
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Cancer cells are typically subject to profound metabolic alterations, including the Warburg effect wherein cancer cells oxidize a decreased fraction of the pyruvate generated from glycolysis. We show herein that the mitochondrial pyruvate carrier (MPC), composed of the products of the MPC1 and MPC2 genes, modulates fractional pyruvate oxidation. MPC1 is deleted or underexpressed in multiple cancers and correlates with poor prognosis. Cancer cells re-expressing MPC1 and MPC2 display increased mitochondrial pyruvate oxidation, with no changes in cell growth in adherent culture. MPC re-expression exerted profound effects in anchorage-independent growth conditions, however, including impaired colony formation in soft agar, spheroid formation, and xenograft growth. We also observed a decrease in markers of stemness and traced the growth effects of MPC expression to the stem cell compartment. We propose that reduced MPC activity is an important aspect of cancer metabolism, perhaps through altering the maintenance and fate of stem cells.
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Cancer cells repress MPC1 to promote the Warburg Effect, and myocytes of diabetic mice elevate glucose consumption in response to MPC inhibition.
“This shift is evident in cancer cells, which repress MPC1 to promote the Warburg Effect, and in myocytes of diabetic mice, which elevate glucose consumption in response to MPC inhibition22,23”
From The multifaceted contributions of mitochondria to cellular metabolism (2018) · cites this paper as [22]
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- Authors
- Schell, J. C., Olson, K. A., Jiang, L., Hawkins, A. J., Van Vranken, J. G., Xie, J., Egnatchik, R. A., Earl, E. G., DeBerardinis, R. J., & Rutter, J.
- Affiliations
- University of Utah (US)
- Children's Medical Center (US)
- Cell Signaling Technology (United States) (US)
- Corresponding author
- Rutter, Jared
- Venue
- Molecular Cell
- Publisher
- Elsevier BV
- Published
- 2014-11
- Volume
- 56
- Issue
- 3
- Pages
- 400-413
- ISSN
- 1097-2765 (ISSN-L)
- OpenAlex
- W1983107759
- Cited by
- 363
- References
- 82
- Citations by year
- 2026: 14 · 2025: 19 · 2024: 30 · 2023: 24 · 2022: 39 · 2021: 51 · 2020: 34 · 2019: 29 · 2018: 33 · 2017: 36 · 2016: 29 · 2015: 21 · 2014: 3 · 2013: 1
- FWCI
- 9.50
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Molecular Cell (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (2r01dk071962-05a1)
- National Cancer Institute (R01CA157996, P30CA042014)
- National Institute of General Medical Sciences (R01GM094232)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01 DK-071962, T32DK007115)
- National Center for Research Resources (S10RR026802)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (5T32 HD-07491, T32HD007491)
- 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 › Mitochondrial Function and Pathology
- Keywords
- mitochondrial pyruvate carrier, MPC1, MPC2, Warburg effect, pyruvate oxidation, cancer metabolism, colon cancer, anchorage-independent growth, tumor spheroids, cancer stem cells, cancer stemness, tumor growth
- MeSH terms
- Animals, Colonic Neoplasms, Glycolysis, Humans, Mice, Nude, Mitochondria, Neoplasm Transplantation, Oxidation-Reduction, HT29 Cells, Mitochondrial Proteins, Anion Transport Proteins, Monocarboxylic Acid Transporters, Mitochondrial Membrane Transport Proteins, Cell Proliferation, HEK293 Cells
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.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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