Mitochondrial fidelity and metabolic agility control immune cell fate and function
Michael N. Sack
Michael N. Sack
Published September 18, 2018; First published July 30, 2018
Citation Information: J Clin Invest. 2018;128(9):3651-3661. https://doi.org/10.1172/JCI120845.
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Category: Review Series

Mitochondrial fidelity and metabolic agility control immune cell fate and function

Abstract

Remodeling of mitochondrial metabolism plays an important role in regulating immune cell fate, proliferation, and activity. Furthermore, given their bacterial ancestry, disruption in mitochondrial fidelity leading to extravasation of their content initiates and amplifies innate immune surveillance with a myriad of physiologic and pathologic consequences. Investigations into the role of mitochondria in the immune system have come to the fore, and appreciation of mitochondrial function and quality control in immune regulation has enhanced our understanding of disease pathogenesis and identified new targets for immune modulation. This mitochondria-centered Review focuses on the role of mitochondrial metabolism and fidelity, as well as the role of the mitochondria as a structural platform, for the control of immune cell polarity, activation, and signaling. Mitochondria-linked disease and mitochondrially targeted therapeutic strategies to manage these conditions are also discussed.

Authors

Michael N. Sack

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Figure 1

Overview of metabolic remodeling with immune cell differentiation and activation.

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Overview of metabolic remodeling with immune cell differentiation and ac...
Overview of metabolic remodeling with immune cell differentiation and activation. (A) Major pathways linked to immunometabolism include the generation of ATP from cytosolic glycolysis or from oxidative phosphorylation of pyruvate, fatty acids, and glutamine. Cytosolic NADPH oxidase or mitochondria produce ROS, which can signal, oxidize proteins, or exert antimicrobial effects. The major sites of mitochondrial ROS production linked to immunometabolism are generated at complexes I and III of the ETC. (B) In monocytes, metabolic remodeling is most extensively characterized in the differentiation into the M1 and M2 cell fates. In CD4+ T cells, immunometabolism has been explored at multiple levels of differentiation, proliferation, activation, and migration. B cell immunometabolic control is less well explored; however, metabolic remodeling is important for different B cell fates. FAO, fatty acid oxidation; Glut Ox, glutamine oxidation; Gly, glycolysis; GO, glucose oxidation; PPP, pentose phosphate pathway; RET, reverse electron transport in the electron transfer chain for ROS generation.