Mitochondrial metabolites: undercover signalling molecules
Open accessAbstract
Mitochondria are one of most characterized metabolic hubs of the cell. Here, crucial biochemical reactions occur and most of the cellular adenosine triphosphate (ATP) is produced. In addition, mitochondria act as signalling platforms and communicate with the rest of the cell by modulating calcium fluxes, by producing free radicals, and by releasing bioactive proteins. It is emerging that mitochondrial metabolites can also act as second messengers and can elicit profound (epi)genetic changes. This review describes the many signalling functions of mitochondrial metabolites under normal and stress conditions, focusing on metabolites of the tricarboxylic acid cycle. We provide a new framework for understanding the role of mitochondrial metabolism in cellular pathophysiology.
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CDKN2A (P16) is hypermethylated and suppressed in tumours of HLRCC patients.
“Consistent with an important role of senescence bypass for the development of tumorigenesis, recent data in HLRCC patients showed that CDKN2A (also known as P16), a key player in senescence, is hypermethylated and suppressed in tumours85.”
From Coupling Krebs cycle metabolites to signalling in immunity and cancer (2018) · cites this paper as [85]
FH-deficient renal cancers are characterised by a distinct DNA hypermethylation phenotype affecting CDK2NA.
“Of note, FH-deficient renal cancers are characterised by a distinct DNA hypermethylation phenotype, which also affects the tumour suppressor CDK2NA85”
From Coupling Krebs cycle metabolites to signalling in immunity and cancer (2018) · cites this paper as [85]
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References 58 · Cited by 136
- Authors
- Frezza, C.
- Affiliations
- University of Cambridge (GB)
- Corresponding author
- Frezza, Christian
- ORCID
- Frezza, Christian
- Venue
- Interface Focus
- Publisher
- The Royal Society
- Published
- 2017-04-06
- Volume
- 7
- Issue
- 2
- Pages
- 20160100
- ISSN
- 2042-8898 (ISSN-L)
- 2042-8901
- PMC
- PMC5311903
- OpenAlex
- W2588603076
- Cited by
- 136
- References
- 58
- Citations by year
- 2026: 6 · 2025: 9 · 2024: 24 · 2023: 10 · 2022: 16 · 2021: 23 · 2020: 19 · 2019: 11 · 2018: 12 · 2017: 6
- FWCI
- 1.23
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Interface Focus (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Apollo (University of Cambridge) (submittedVersion, cc-by)
- Apollo (cc-by)
- Funders
- Medical Research Council (Core Fund to the MRC Cancer Unit)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolomics and Mass Spectrometry Studies
- Keywords
- mitochondrial metabolites, mitochondrial signalling, second messengers, TCA cycle, mitochondrial metabolism, calcium signaling, reactive oxygen species, epigenetic regulation, cellular stress, ATP production
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