2-Oxoglutarate-dependent dioxygenases are sensors of energy metabolism, oxygen availability, and iron homeostasis: potential role in the regulation of aging process
Open accessAbstract
Recent studies have revealed that the members of an ancient family of nonheme Fe(2+)/2-oxoglutarate-dependent dioxygenases (2-OGDO) are involved in the functions associated with the aging process. 2-Oxoglutarate and O2 are the obligatory substrates and Fe(2+) a cofactor in the activation of 2-OGDO enzymes, which can induce the hydroxylation of distinct proteins and the demethylation of DNA and histones. For instance, ten-eleven translocation 1-3 (TET1-3) are the demethylases of DNA, whereas Jumonji C domain-containing histone lysine demethylases (KDM2-7) are the major epigenetic regulators of chromatin landscape, known to be altered with aging. The functions of hypoxia-inducible factor (HIF) prolyl hydroxylases (PHD1-3) as well as those of collagen hydroxylases are associated with age-related degeneration. Moreover, the ribosomal hydroxylase OGFOD1 controls mRNA translation, which is known to decline with aging. 2-OGDO enzymes are the sensors of energy metabolism, since the Krebs cycle intermediate 2-oxoglutarate is an activator whereas succinate and fumarate are the potent inhibitors of 2-OGDO enzymes. In addition, O2 availability and iron redox homeostasis control the activities of 2-OGDO enzymes in tissues. We will briefly elucidate the catalytic mechanisms of 2-OGDO enzymes and then review the potential functions of the above-mentioned 2-OGDO enzymes in the control of the aging process.
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Germline mutations in L2HGDH and D2HGDH cause L-2-hydroxyglutaric aciduria and D-2-hydroxyglutaric aciduria.
“The cause of these so-called 2-hydroxyglutaric acidurias (2HGAs) was attributed to germline mutations in L-2-HG dehydrogenase (L2HGDH) and D-2-HG dehydrogenase (D2HGDH), the mitochondrial enzymes responsible for the conversion of 2-HG to α-KG and thus its breakdown107-109.”
From Coupling Krebs cycle metabolites to signalling in immunity and cancer (2018) · cites this paper as [109]
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Kladchenko, E. S., Lavrichenko, D. S., Uppe, V. A., Bogacheva, E. A., Vodiasova, E. A., & Chelebieva, E. S. (2026) · Veterinary Sciences · doi:10.3390/vetsci13101051
- Authors
- Salminen, A., Kauppinen, A., & Kaarniranta, K.
- Affiliations
- University of Eastern Finland (FI)
- Corresponding author
- Kaarniranta, Kai
- Venue
- Cellular and Molecular Life Sciences
- Published
- 2015-06-29
- Volume
- 72
- Issue
- 20
- Pages
- 3897-3914
- ISSN
- 1420-682X (ISSN-L)
- 1420-9071
- PMC
- PMC11114064
- OpenAlex
- W1010999108
- Cited by
- 99
- References
- 216
- Citations by year
- 2026: 6 · 2025: 4 · 2024: 9 · 2023: 12 · 2022: 11 · 2021: 7 · 2020: 12 · 2019: 6 · 2018: 10 · 2017: 10 · 2016: 9 · 2015: 3
- FWCI
- 0.42
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Cellular and Molecular Life Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Kuopion Yliopistollinen Sairaala
- Topics
- Physical Sciences › Chemistry › Inorganic Chemistry › Metal-Catalyzed Oxygenation Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Keywords
- 2-oxoglutarate-dependent dioxygenase, aging, energy metabolism, oxygen availability, iron homeostasis, histone demethylation, DNA demethylation, mRNA translation, epigenetic regulation
- MeSH terms
- Aging, Animals, Hypoxia, Energy Metabolism, Homeostasis, Iron, Oxygen, Protein Biosynthesis, DNA Methylation, Epigenesis, Genetic, Dioxygenases
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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