Cited by 399Cancer, Hypoxia, and MetabolismCancer, Lipids, and MetabolismMitochondrial Function and Pathology

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Mitochondria as biosynthetic factories for cancer proliferation

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Ahn, Christopher S, Metallo, Christian M·2015·Cancer & Metabolism

DOI 10.1186/s40170-015-0128-2PMC PMC4305394

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Abstract

Unchecked growth and proliferation is a hallmark of cancer, and numerous oncogenic mutations reprogram cellular metabolism to fuel these processes. As a central metabolic organelle, mitochondria execute critical biochemical functions for the synthesis of fundamental cellular components, including fatty acids, amino acids, and nucleotides. Despite the extensive interest in the glycolytic phenotype of many cancer cells, tumors contain fully functional mitochondria that support proliferation and survival. Furthermore, tumor cells commonly increase flux through one or more mitochondrial pathways, and pharmacological inhibition of mitochondrial metabolism is emerging as a potential therapeutic strategy in some cancers. Here, we review the biosynthetic roles of mitochondrial metabolism in tumors and highlight specific cancers where these processes are activated.

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Figure 1 Biosynthetic nodes within mitochondria. Metabolic pathways within mitochondria that contribute to biosynthesis in cancer and other proliferating cells. TCA metabolism and FOCM enable cells to convert carbohydrates and amino acids to lipids, non-essential amino acids, nucleotides (including purines used for cofactor synthesis), glutathione, heme, and other cellular components. Critical biosynthetic routes are indicated by yellow arrows. Enzymatic reactions that are dependent on redox-sensitive cofactors are depicted in red.CC BY · PubMed Central

Figure 2 Coordination of carbon and nitrogen metabolism across amino acids. Glutamate and aKG are key substrates in numerous transamination reactions and can also serve as precursors for glutamine, proline, and the TCA cycle. Mitochondrial enzymes catalyzing these reactions are highlighted in blue, and TCA cycle intermediates are highlighted in orange (pyruvate enters the TCA cycle as acetyl-CoA or oxaloacetate).CC BY · PubMed Central

Figure 3 Biosynthetic sources for purine and pyrimidine synthesis. Sources and fates of nitrogen, carbon, and oxygen atoms are colored as indicated. Italicized metabolites can be sourced from the mitochondria or cytosol. The double bond formed by the action of DHODH/ubiquinone is also indicated.CC BY · PubMed Central

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Authors: Ahn, C. S., & Metallo, C. M.
Affiliations: University of California San Diego (US)
Corresponding author: Metallo, Christian M
ORCID: Ahn, Christopher S
Metallo, Christian M
Venue: Cancer & Metabolism
Publisher: Springer Science and Business Media LLC
Published: 2015-01-25
Volume: 3
Issue: 1
Pages: 1-1
ISSN: 2049-3002 (ISSN-L)
DOI: 10.1186/s40170-015-0128-2
PMC: PMC4305394
OpenAlex: W2157099092
Cited by: 399
References: 84
Citations by year: 2026: 16 · 2025: 28 · 2024: 33 · 2023: 28 · 2022: 35 · 2021: 58 · 2020: 41 · 2019: 41 · 2018: 31 · 2017: 43 · 2016: 33 · 2015: 12
FWCI: 13.12
Type: journal article
Language: en
Open access: gold
doi.org
Licence: cc-by
creativecommons.org/licenses/by/4.0 (unspecified)
Locations: Cancer & Metabolism (publishedVersion, cc-by)
Europe PMC (PubMed Central) (publishedVersion, cc-by)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
eScholarship (California Digital Library) (submittedVersion)
Funders: U.S. Department of Defense (W81XWH, W81XWH1310105, W81XWH-13)
National Institutes of Health (W81XWH)
National Cancer Institute (R01CA132847, R01CA188652)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Lipids, and Metabolism
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
Keywords: mitochondrial metabolism, tumor cell proliferation, biosynthesis, fatty acid synthesis, amino acid synthesis, nucleotide synthesis, cancer metabolism, mitochondrial dysfunction, metabolic reprogramming, cancer therapy

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Mitochondria as biosynthetic factories for cancer proliferation

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