Document Type
Article
Publication Date
5-26-2025
Original Citation
West A,
McGuire P.
Tipping the balance: innate and adaptive immunity in mitochondrial disease. Curr Opin Immunol. 2025;95:102566.
Keywords
JMG
JAX Source
Curr Opin Immunol. 2025;95:102566.
ISSN
1879-0372
PMID
40424975
DOI
https://doi.org/10.1016/j.coi.2025.102566
Grant
This research was supported by awards W81XWH-17-1- 0052 and W81XWH-20-1-0150 to A.P.W. from the Office of the Assistant Secretary of Defense and for Health Affairs through the Peer Reviewed Medical Research Programs. Additional support was provided by NIH (USA) grant R01HL148153 to A.P.W.
Abstract
Mitochondrial diseases (MtD) provide a unique window into the complex interplay between metabolism and immune function. These rare disorders, caused by defects in oxidative phosphorylation, result in bioenergetic deficiencies that disrupt multiple organ systems. While traditionally studied for their metabolic impact, MtD also profoundly affect the immune system, altering both innate and adaptive responses. This review explores how mitochondrial dysfunction shapes immune dysregulation, influencing thymocyte maturation, regulatory T cells, and B cell function while also driving innate immune activation through mitochondrial DNA instability and type I interferon signaling. Additionally, MtD highlight an emerging overlap between inborn errors of metabolism and inborn errors of immunity, revealing shared pathways that connect mitochondrial dysfunction to immune deficiencies and inflammatory disease. Studying MtD not only advances our understanding of immunometabolism but also provides critical insights into more common inflammatory and autoimmune conditions, offering potential therapeutic targets that extend beyond rare mitochondrial disorders.
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.