Mitochondrial Complex II in the regulation of immunopathology.

Authors

Akira Yamamoto, Yuichi Sumii, Pavan Reddy

Published in

Trends in immunology. Aug 18, 2026. Epub Aug 18, 2026.

Abstract

Mitochondrial complex II, succinate dehydrogenase (SDH), links the tricarboxylic acid cycle to the electron transport chain by oxidizing succinate to fumarate and reducing ubiquinone. This unusual position gives Complex II control over bioenergetics, redox state, succinate signaling, and chromatin regulation. In immune cells, Complex II regulates macrophage responses via the succinate-hypoxia-inducible factor-1α-IL-1β axis, T-cell proliferation, lineage commitment, and cytotoxicity. In target tissues of an aberrant immune attack, such as the intestinal epithelium and stem-cell compartments, SDHA loss lowers tissue tolerance, promotes inflammatory memory through succinate-driven epigenetic reprogramming, and amplifies immune-mediated injury. In tumors, SDH loss increases antigen presentation and their susceptibility to T-cell killing. Complex II, therefore, regulates immunopathology through its actions within both attacking immune cells and injured target tissues.

PMID:
42613239
Bibliographic data and abstract were imported from PubMed on 19 Aug 2026.

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