Mitochondria as disease-relevant organelles in rheumatoid arthritis

Cornelia M. Weyand, Bowen Wu, Tao Huang, Zhaolan Hu, Jörg J. Goronzy

Research output: Contribution to journalReview articlepeer-review


Mitochondria are the controllers of cell metabolism and are recognized as decision makers in cell death pathways, organizers of cytoplasmic signaling networks, managers of cellular stress responses, and regulators of nuclear gene expression. 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 naïve 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.

Original languageEnglish (US)
Pages (from-to)208-223
Number of pages16
JournalClinical and Experimental Immunology
Issue number3
StatePublished - Mar 2023


  • T cells
  • autoimmunity
  • macrophages
  • mitochondria
  • rheumatoid arthritis
  • tumor necrosis factor

ASJC Scopus subject areas

  • General Medicine


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