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Krebs cycle rewired for macrophage and dendritic cell effector functions

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,...

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Published in:	FEBS letters 2017-10, Vol.591 (19), p.2992-3006
Main Authors:	Ryan, Dylan Gerard, O'Neill, Luke A. J.
Format:	Article
Language:	English
Subjects:	citrate Citric Acid Cycle cytokines dendritic cell Dendritic Cells - metabolism Epigenesis, Genetic fumarate Humans inflammation Inflammation - metabolism Inflammation - pathology itaconate Krebs cycle macrophage Macrophages - metabolism Models, Biological succinate
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description	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.
doi_str_mv	10.1002/1873-3468.12744
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subjects	citrate Citric Acid Cycle cytokines dendritic cell Dendritic Cells - metabolism Epigenesis, Genetic fumarate Humans inflammation Inflammation - metabolism Inflammation - pathology itaconate Krebs cycle macrophage Macrophages - metabolism Models, Biological succinate
title	Krebs cycle rewired for macrophage and dendritic cell effector functions
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