柠檬酸循环
生物
代谢途径
免疫系统
疾病
癌变
重编程
谷氨酰胺分解
免疫
癌症
计算生物学
细胞
细胞生物学
生物化学
新陈代谢
免疫学
遗传学
医学
病理
作者
Dylan Gerard Ryan,Michael P. Murphy,Christian Frezza,Hiran A. Prag,Edward T. Chouchani,Luke A.J. O’Neill,Evanna L. Mills
标识
DOI:10.1038/s42255-018-0014-7
摘要
Metabolic reprogramming has become a key focus for both immunologists and cancer biologists, with exciting advances providing new insights into underlying mechanisms of disease. Metabolites traditionally associated with bioenergetics or biosynthesis have been implicated in immunity and malignancy in transformed cells, with a particular focus on intermediates of the mitochondrial pathway known as the Krebs cycle. Among these, the intermediates succinate, fumarate, itaconate, 2-hydroxyglutarate isomers (D-2-hydroxyglutarate and L-2-hydroxyglutarate) and acetyl-CoA now have extensive evidence for "non-metabolic" signalling functions in both physiological immune contexts and in disease contexts, such as the initiation of carcinogenesis. This review will describe how metabolic reprogramming, with emphasis placed on these metabolites, leads to altered immune cell and transformed cell function. The latest findings are informative for new therapeutic approaches which could be transformative for a range of diseases.
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