Metabolic Coordination of Cell Fate by α-Ketoglutarate-Dependent Dioxygenases

被引：89

作者：

Baksh, Sanjeethan C. ^{[1
]}

Finley, Lydia W. S. ^{[2
,3
]}

机构：

[1] Rockefeller Univ, Robin Chemers Neustein Lab Mammalian Cell Biol &, Howard Hughes Med Inst, New York, NY USA

[2] Mem Sloan Kettering Canc Ctr, Cell Biol Program, New York, NY 10021 USA

[3] Mem Sloan Kettering Canc Ctr, Ctr Epigenet Res, New York, NY 10021 USA

来源：

TRENDS IN CELL BIOLOGY | 2021年 / 31卷 / 01期

基金：

美国国家卫生研究院;

关键词：

ACUTE MYELOID-LEUKEMIA; NEURAL STEM-CELLS; IDH2; MUTATIONS; TET2; FUNCTION; BONE-MARROW; T-CELLS; HISTONE; DIFFERENTIATION; FUMARATE; ACTIVATION;

D O I：

10.1016/j.tcb.2020.09.010

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Cell fate determination requires faithful execution of gene expression programs, which are increasingly recognized to respond to metabolic inputs. In particular, the family of alpha-ketoglutarate (alpha KG)-dependent dioxygenases, which include several chromatin-modifying enzymes, are emerging as key mediators of metabolic control of cell fate. alpha KG-dependent dioxygenases consume the metabolite alpha KG (also known as 2-oxoglutarate) as an obligate cosubstrate and are inhibited by succinate, fumarate, and 2-hydroxyglutarate. Here, we review the role of these metabolites in the control of dioxygenase activity and cell fate programs. We discuss the biochemical and transcriptional mechanisms enabling these metabolites to control cell fate and review evidence that nutrient availability shapes tissue-specific fate programs via alpha KG-dependent dioxygenases.

引用

页码：24 / 36

页数：13

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