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, 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.

Ryan DG ，O'Neill LAJ 《-》

A Role for the Krebs Cycle Intermediate Citrate in Metabolic Reprogramming in Innate Immunity and Inflammation.

Williams NC ，O'Neill LAJ 《Frontiers in Immunology》

Krebs Cycle Rewired: Driver of Atherosclerosis Progression?

The tricarboxylic acid (TCA) cycle is the center of energy metabolism in eukaryotic cells and is dynamically adjusted according to the energy needs of cells. Macrophages are activated by inflammatory stimuli, and then two breakpoints in TCA cycle lead to the accumulation of intermediates. Atherosclerosis is a chronic inflammatory process. Here, the "non-metabolic" signaling functions of TCA cycle intermediates in the macrophage under inflammatory stimulation and the role of intermediates in the progression of atherosclerosis are discussed.

Liang Y ，Chen Y ，Li L ，Zhang S ，Xiao J ，Wei D ... -  《-》

Krebs Cycle Reborn in Macrophage Immunometabolism.

Ryan DG ，O'Neill LAJ 《-》

Coupling Krebs cycle metabolites to signalling in immunity and cancer.

Ryan DG ，Murphy MP ，Frezza C ，Prag HA ，Chouchani ET ，O'Neill LA ，Mills EL ... -  《Nature metabolism》