期刊
FEBS LETTERS
卷 591, 期 19, 页码 2992-3006出版社
WILEY
DOI: 10.1002/1873-3468.12744
关键词
citrate; cytokines; dendritic cell; fumarate; inflammation; itaconate; Krebs cycle; macrophage; succinate
资金
- Wellcome Trust [109443/Z/15/Z] Funding Source: Medline
- Wellcome Trust [109443/Z/15/Z] Funding Source: Wellcome Trust
The Krebs cycle is an amphibolic pathway operating in the mitochondrial matrix of all eukaryotic organisms. In response to proinflammatory stimuli, macrophages and dendritic cells undergo profound metabolic remodelling to support the biosynthetic and bioenergetic requirements of the cell. Recently, it has been discovered that this metabolic shift also involves the rewiring of the Krebs cycle to regulate cellular metabolic flux and the accumulation of Krebs cycle intermediates, notably, citrate, succinate and fumarate. Interestingly, a new role for Krebs cycle intermediates as signalling molecules and immunomodulators that dictate the inflammatory response has begun to emerge. This review will discuss the latest developments in Krebs cycle rewiring and immune cell effector functions, with a particular focus on the regulation of cytokine production.
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