REVIEW: Metabolic ROS Signaling: To Immunity and Beyond

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A. Y. Andreyev^1,a*, Y. E. Kushnareva^2,b, N. N. Starkova^3,c, and A. A. Starkov^4,d

¹The Scripps Research Institute, 10550 N Torrey Pines Rd, La Jolla, CA 92037, USA

²La Jolla Institute for Allergy and Immunology, 9420 Athena Circle, La Jolla, CA 92037, USA

³State University of New York, Maritime College, New York, NY 10465, USA

⁴Brain and Mind Research Institute, Weill Medical College of Cornell University, New York, NY 10065, USA

^* To whom correspondence should be addressed.

Received September 11, 2020; Revised November 13, 2020; Accepted November 17, 2020

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Metabolism is a critical determinant of immune cell functionality. Immunometabolism, by definition, is a multidisciplinary area of immunology research that integrates the knowledge of energy transduction mechanisms and biochemical pathways. An important concept in the field is metabolic switch, a transition of immune cells upon activation to preferential utilization of select catabolic pathways for their energy needs. Mitochondria are not inert in this process and contribute to the metabolic adaptation by different mechanisms which include increasing ATP production to match dynamic bioenergetic demands and serving as a signaling platform. The latter involves generation of reactive oxygen species (ROS), one of the most intensively studied mitochondrial processes. While the role of mitochondrial ROS in the context of oxidative stress is well established, ROS signaling in immunity is an emerging and quickly changing field. In this review, we discuss ROS signaling and immunometabolism concepts from the standpoint of bioenergetics. We also provide a critical insight into the methodology for ROS assessment, outlining current challenges in the field. Finally, based on our analysis of the literature data, we hypothesize that regulatory ROS production, as opposed to oxidative stress, is controlled by mitochondrial biogenesis rather than metabolic switches.

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KEY WORDS: immunometabolism, reactive oxygen species, glycolytic switch, macrophages, T cells, mitochondrial biogenesis

DOI: 10.1134/S0006297920120160

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