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The Roles of 2-Hydroxyglutarate

Journal

Publisher

FRONTIERS MEDIA SA
DOI: 10.3389/fcell.2021.651317

Keywords

2-Hydroxyglutarate; epigenetics; metabolism; immunology; isocitrate dehydrogenase

Funding

  1. National Natural Science Foundation of China [82025026, 81730077]
  2. National Key R&D Program of China [2016YFC1302301]
  3. Science and Technology Program of Guangzhou [201704020095]
  4. Program for Guangdong Introducing Innovative and Entrepreneurial Teams [2016ZT06S252]
  5. Fundamental Research Funds for the Central Universities [17ykjc14]

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2-HG plays a significant role in 2-hydroxyglutaric aciduria, tumors with IDH1/2mt mutations, and ccRCC, being regarded as an oncometabolite. It can also accumulate in hypoxic or acidic pH conditions, and has been shown to have a vital role in the fate decision of immune cells.
2-Hydroxyglutarate (2-HG) is structurally similar to alpha-ketoglutarate (alpha-KG), which is an intermediate product of the tricarboxylic acid (TCA) cycle; it can be generated by reducing the ketone group of alpha-KG to a hydroxyl group. The significant role that 2-HG plays has been certified in the pathophysiology of 2-hydroxyglutaric aciduria (2HGA), tumors harboring mutant isocitrate dehydrogenase 1/2 (IDH1/2mt), and in clear cell renal cell carcinoma (ccRCC). It is taken as an oncometabolite, raising much attention on its oncogenic mechanism. In recent years, 2-HG has been verified to accumulate in the context of hypoxia or acidic pH, and there are also researches confirming the vital role that 2-HG plays in the fate decision of immune cells. Therefore, 2-HG not only participates in tumorigenesis. This text will also summarize 2-HG's identities besides being an oncometabolite and will discuss their enlightenment for future research and clinical treatment.

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