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SDHA: a key player in T cell-mediated intestinal disease severity

Cellular & Molecular Immunology volume 19, pages 139–141 (2022)Cite this article

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In their recent article in Nature Immunology, Fujiwara et al. identified reduced mitochondrial respiration and increased succinate levels in intestinal epithelial cells (IECs) from several distinct models of T cell-mediated colitis. Their observations point to a specific link between alterations in the mitochondrial complex II component SDHA and the severity of T cell-mediated intestinal diseases and suggest that SDHA dysfunction could be a diagnostic and/or prognostic biomarker in T cell-mediated immunopathology.

Unique metabolic phenotypes are characteristic of several human pathologies, which is hardly surprising given the known interplay between cellular metabolism and gene expression regulation, posttranslational modification and cell signaling. The last decade has brought a greater appreciation of the metabolic control of immune function, known as immunometabolism [1], coinciding with a renaissance in the study of mitochondria as critical hubs of not only energy production but also cell fate, with important implications in human health [2]. Indeed, mitochondria are increasingly recognized for their involvement in metabolic reprogramming and integrating host- and microbial-derived signals––for example, gastrointestinal diseases such as inflammatory bowel diseases (IBDs) and colorectal cancer are characterized by alterations in intestinal stemness, the microbiota and mitochondrial metabolism [3]. Mitochondrial function thus emerges at the interface of health and disease, and its breakdown can trigger aberrant tissue responses. However, the mechanistic understanding of the causal role of mitochondrial fitness in noninfectious intestinal pathologies is limited, and therapies targeting mitochondrial (dys)function are currently lacking.

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Fig. 1: SDHA downregulation exacerbates the severity of T cell-mediated immunopathology associated with graft-versus-host disease.

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Acknowledgements

Research in the author’s laboratory is supported by the Ministry of Science and Innovation and the Spanish Research Agency through FEDER funds (RTI2018-098517-B100) (MICINN/AEI/FEDER, EU). CBMSO receives an institutional grant from the Fundación Ramón Areces and Banco Santander, Spain.

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  1. Centro de Biología Molecular Severo Ochoa. Consejo Superior de Investigaciones Científicas, Universidad Autónoma de Madrid (CSIC/UAM), C/ Nicolás Cabrera 1, Campus de Cantoblanco, 28049, Madrid, Spain

    José M. Izquierdo

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Correspondence to José M. Izquierdo.

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Izquierdo, J.M. SDHA: a key player in T cell-mediated intestinal disease severity. Cell Mol Immunol 19, 139–141 (2022). https://doi.org/10.1038/s41423-021-00820-7

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