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IMMUNOMETABOLISM

Mitochondrial ROS signals prevent excessive immune response

Nature Metabolism volume 3, pages 588–589 (2021)Cite this article

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Reactive oxygen species (ROS) were long considered unwanted and dangerous by-products of mitochondrial metabolism, specifically oxidative phosphorylation. More recently, evidence has indicated that mitochondrial ROS are also essential signalling molecules that unexpectedly promote longevity, through a mechanism termed mitohormesis. In this issue, Timblin et al. expand this concept to immunity, specifically macrophage function, by demonstrating that mitochondrial ROS are required to prevent an excessive immune response.

Macrophages are leukocytes found in essentially all tissues in organisms, particularly humans. These cells not only remove debris and microorganisms by phagocytosis but also play an important role in non-specific immune defence mechanisms, known as innate immunity. Nevertheless, they are also capable of recruiting other immune cells, including lymphocytes, to sites of infection and inflammation, thereby contributing to the specific process of adaptive immunity. Macrophages have long been known to produce ROS via mitochondrial oxidative phosphorylation (OXPHOS) as well as from non-mitochondrial sources, specifically NADPH oxidases located at the cell membrane. In this issue of Nature Metabolism, Timblin et al. show that a transient increase in antimicrobial ROS within the mitochondria of macrophages induces a cascade of defence mechanisms against ROS as well as a shift toward non-oxidative energy metabolism, and subsequently results in lower ROS levels3 (Fig. 1c).

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Fig. 1: Mitohormesis limits an excessive immune response.

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Authors and Affiliations

  1. Energy Metabolism Laboratory, D-HEST, Swiss Federal Institute of Technology (ETH) Zurich, Zurich, Switzerland

    Kim Zarse & Michael Ristow

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  1. Kim Zarse
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  2. Michael Ristow
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Correspondence to Michael Ristow.

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Zarse, K., Ristow, M. Mitochondrial ROS signals prevent excessive immune response. Nat Metab 3, 588–589 (2021). https://doi.org/10.1038/s42255-021-00387-7

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