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Tricarboxylic acid cycle metabolites in the control of macrophage activation and effector phenotypes
Author(s) -
Noe Jordan T.,
Mitchell Robert A.
Publication year - 2019
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1002/jlb.3ru1218-496r
Subject(s) - citric acid cycle , biology , effector , tricarboxylic acid , microbiology and biotechnology , macrophage polarization , macrophage , metabolism , metabolic pathway , context (archaeology) , phenotype , cell cycle , biochemistry , cell , in vitro , gene , paleontology
The tricarboxylic acid (TCA) cycle is a mitochondrial metabolic hub that coordinates the metabolism of carbohydrates, proteins, and fats into carbon dioxide and ATP. At specific points in the cycle, the diversion, import, or export of TCA metabolites allows for the dynamic regulation of a variety of tissue and/or cell‐specific phenotypic processes. Recent studies have identified that a number of TCA metabolites are important in controlling monocyte/macrophage phenotypes and effector functions while specific macrophage activation or polarization states functionally determine the relative utilization of each. This review focuses on the metabolic reprogramming of the TCA cycle in macrophages and how individual metabolites play a variety of context‐specific roles in determining physiologic and pathologic macrophage activation and homeostatic functions. We discuss the implications of these findings and address unanswered questions regarding the role of the TCA cycle in guiding macrophage‐dependent immune responses.