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Cells of the immune system are particularly dependent on mitochondrial resources, as they must swiftly respond to danger signals with activation, trafficking, migration, and generation of daughter cells. Analogously, faulty immune responses that lead to autoimmunity and tissue inflammation rely on mitochondria to supply energy, cell building blocks and metabolic intermediates. Emerging data endorse the concept that mitochondrial fitness, and the lack of it, is of particular relevance in the autoimmune disease rheumatoid arthritis (RA) where deviations of bioenergetic and biosynthetic flux affect T cells during early and late stages of disease. During early stages of RA, mitochondrial deficiency allows na\u00efve RA T cells to lose self-tolerance, biasing fundamental choices of the immune system toward immune-mediated tissue damage and away from host protection. During late stages of RA, mitochondrial abnormalities shape the response patterns of RA effector T cells engaged in the inflammatory lesions, enabling chronicity of tissue damage and tissue remodeling. In the inflamed joint, autoreactive T cells partner with metabolically reprogrammed tissue macrophages that specialize in antigen-presentation and survive by adapting to the glucose-deplete tissue microenvironment. Here, we summarize recent data on dysfunctional mitochondria and mitochondria-derived signals relevant in the RA disease process that offer novel opportunities to deter autoimmune tissue inflammation by metabolic interference.<\/jats:p>","DOI":"10.1093\/cei\/uxac107","type":"journal-article","created":{"date-parts":[[2022,11,24]],"date-time":"2022-11-24T08:45:59Z","timestamp":1669279559000},"page":"208-223","source":"Crossref","is-referenced-by-count":27,"title":["Mitochondria as disease-relevant organelles in rheumatoid arthritis"],"prefix":"10.1093","volume":"211","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2230-9802","authenticated-orcid":false,"given":"Cornelia M","family":"Weyand","sequence":"first","affiliation":[{"name":"Department of Medicine, Mayo Clinic Alix School of Medicine , Rochester, MN 55905 , USA"},{"name":"Department of Medicine, Stanford University School of Medicine , Stanford, CA 94305 , 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