The Roles of 2-Hydroxyglutarate

被引：94

作者：

Du, Xin ^{[1
,2
]}

Hu, Hai ^{[1
,2
]}

机构：

[1] Sun Yat Sen Univ, Sun Yat Sen Mem Hosp, Guangdong Prov Key Lab Malignant Tumor Epigenet &, Guangzhou, Peoples R China

[2] Sun Yat Sen Univ, Sun Yat Sen Mem Hosp, Dept Oncol, Guangzhou, Peoples R China

来源：

FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY | 2021年 / 9卷

基金：

中国国家自然科学基金; 国家重点研发计划;

关键词：

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

D O I：

10.3389/fcell.2021.651317

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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.

引用

页数：13

共 120 条

[11] Isocitrate dehydrogenase 1 and 2 mutations induce BCL-2 dependence in acute myeloid leukemia [J].

Chan, Steven M. ;

Thomas, Daniel ;

Corces-Zimmerman, M. Ryan ;

Xavy, Seethu ;

Rastogi, Suchita ;

Hong, Wan-Jen ;

Zhao, Feifei ;

Medeiros, Bruno C. ;

Tyvoll, David A. ;

Majeti, Ravindra .

NATURE MEDICINE, 2015, 21 (02) :178-184

[12] Mutant IDH1 promotes leukemogenesis in vivo and can be specifically targeted in human AML [J].

Chaturvedi, Anuhar ;

Cruz, Michelle Maria Araujo ;

Jyotsana, Nidhi ;

Sharma, Amit ;

Yun, Haiyang ;

Goerlich, Kerstin ;

Wichmann, Martin ;

Schwarzer, Adrian ;

Preller, Matthias ;

Thol, Felicitas ;

Meyer, Johann ;

Haemmerle, Reinhard ;

Struys, Eduard A. ;

Jansen, Erwin E. ;

Modlich, Ute ;

Li, Zhixiong ;

Sly, Laura M. ;

Geffers, Robert ;

Lindner, Robert ;

Manstein, Dietmar J. ;

Lehmann, Ulrich ;

Krauter, Juergen ;

Ganser, Arnold ;

Heuser, Michael .

BLOOD, 2013, 122 (16) :2877-2887

[13] Cancer-associated IDH2 mutants drive an acute myeloid leukemia that is susceptible to Brd4 inhibition [J].

Chen, Chong ;

Liu, Yu ;

Lu, Chao ;

Cross, Justin R. ;

Morris, John P. ;

Shroff, Aditya S. ;

Ward, Patrick S. ;

Bradner, James E. ;

Thompson, Craig ;

Lowe, Scott W. .

GENES & DEVELOPMENT, 2013, 27 (18) :1974-1985

[14] Oncometabolites D- and L-2-Hydroxyglutarate Inhibit the AIkB Family DNA Repair Enzymes under Physiological Conditions [J].

Chen, Fangyi ;

Bian, Ke ;

Tang, Qi ;

Fedeles, Bogdan I. ;

Singh, Vipender ;

Humulock, Zachary T. ;

Essigmann, John M. ;

Li, Deyu .

CHEMICAL RESEARCH IN TOXICOLOGY, 2017, 30 (04) :1102-1110

[15] Lactate dehydrogenase A silencing in IDH mutant gliomas [J].

Chesnelong, Charles ;

Chaumeil, Myriam M. ;

Blough, Michael D. ;

Al-Najjar, Mohammad ;

Stechishin, Owen D. ;

Chan, Jennifer A. ;

Pieper, Russell O. ;

Ronen, Sabrina M. ;

Weiss, Samuel ;

Luchman, H. Artee ;

Cairncross, J. Gregory .

NEURO-ONCOLOGY, 2014, 16 (05) :686-695

[16] The prognostic impact and stability of Isocitrate dehydrogenase 2 mutation in adult patients with acute myeloid leukemia [J].

Chou, W-C ;

Lei, W-C ;

Ko, B-S ;

Hou, H-A ;

Chen, C-Y ;

Tang, J-L ;

Yao, M. ;

Tsay, W. ;

Wu, S-J ;

Huang, S-Y ;

Hsu, S-C ;

Chen, Y-C ;

Chang, Y-C ;

Kuo, K-T ;

Lee, F-Y ;

Liu, M-C ;

Liu, C-W ;

Tseng, M-H ;

Huang, C-F ;

Tien, H-F .

LEUKEMIA, 2011, 25 (02) :246-253

[17] The oncometabolite 2-hydroxyglutarate inhibits histone lysine demethylases [J].

Chowdhury, Rasheduzzaman ;

Yeoh, Kar Kheng ;

Tian, Ya-Min ;

Hillringhaus, Lars ;

Bagg, Eleanor A. ;

Rose, Nathan R. ;

Leung, Ivanhoe K. H. ;

Li, Xuan S. ;

Woon, Esther C. Y. ;

Yang, Ming ;

McDonough, Michael A. ;

King, Oliver N. ;

Clifton, Ian J. ;

Klose, Robert J. ;

Claridge, Timothy D. W. ;

Ratcliffe, Peter J. ;

Schofield, Christopher J. ;

Kawamura, Akane .

EMBO REPORTS, 2011, 12 (05) :463-469

[18] Hypoxia-induced reactive oxygen species formation in skeletal muscle [J].

Clanton, Thomas L. .

JOURNAL OF APPLIED PHYSIOLOGY, 2007, 102 (06) :2379-2388

[19] Preleukemic mutations in human acute myeloid leukemia affect epigenetic regulators and persist in remission [J].

Corces-Zimmerman, M. Ryan ;

Hong, Wan-Jen ;

Weissman, Irving L. ;

Medeiros, Bruno C. ;

Majeti, Ravindra .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2014, 111 (07) :2548-2553

[20] Systematic sequencing of renal carcinoma reveals inactivation of histone modifying genes [J].

Dalgliesh, Gillian L. ;

Furge, Kyle ;

Greenman, Chris ;

Chen, Lina ;

Bignell, Graham ;

Butler, Adam ;

Davies, Helen ;

Edkins, Sarah ;

Hardy, Claire ;

Latimer, Calli ;

Teague, Jon ;

Andrews, Jenny ;

Barthorpe, Syd ;

Beare, Dave ;

Buck, Gemma ;

Campbell, Peter J. ;

Forbes, Simon ;

Jia, Mingming ;

Jones, David ;

Knott, Henry ;

Kok, Chai Yin ;

Lau, King Wai ;

Leroy, Catherine ;

Lin, Meng-Lay ;

McBride, David J. ;

Maddison, Mark ;

Maguire, Simon ;

McLay, Kirsten ;

Menzies, Andrew ;

Mironenko, Tatiana ;

Mulderrig, Lee ;

Mudie, Laura ;

O'Meara, Sarah ;

Pleasance, Erin ;

Rajasingham, Arjunan ;

Shepherd, Rebecca ;

Smith, Raffaella ;

Stebbings, Lucy ;

Stephens, Philip ;

Tang, Gurpreet ;

Tarpey, Patrick S. ;

Turrell, Kelly ;

Dykema, Karl J. ;

Khoo, Sok Kean ;

Petillo, David ;

Wondergem, Bill ;

Anema, John ;

Kahnoski, Richard J. ;

Teh, Bin Tean ;

Stratton, Michael R. .

NATURE, 2010, 463 (7279) :360-363

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