Mitochondria regulate endoplasmic reticulum (ER) size and protein maturation in healthy cells by releasing aspartate, regenerating cytoplasmic NAD+ and ADP-ribosylating the ER stress sensor BiP. In the autoimmune disease rheumatoid arthritis, a deficiency in mitochondrial aspartate in T cells causes an increase in ER size and excess production of the inflammatory mediator tumor necrosis factor (TNF), driving tissue inflammation.
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References
Weyand, C. M. & Goronzy, J. J. The immunology of rheumatoid arthritis. Nat. Immunol. 22, 10–18 (2021). A Review article on the immunological mechanisms of RA.
Feldmann, M. & Maini, R. N. Lasker Clinical Medical Research Award. TNF defined as a therapeutic target for rheumatoid arthritis and other autoimmune diseases. Nat. Med. 9, 1245–1250 (2003). A commentary on the Lasker award describing the success of TNF inhibition as an interventional treatment for autoimmune diseases.
Li, Y. et al. The DNA repair nuclease MRE11A functions as a mitochondrial protector and prevents T cell pyroptosis and tissue inflammation. Cell Metab. 30, 477–492 (2019). This paper mechanistically links tissue inflammation to impaired mitochondrial DNA repair.
Wen, Z. et al. N-myristoyltransferase deficiency impairs activation of kinase AMPK and promotes synovial tissue inflammation. Nat. Immunol. 20, 313–325 (2019). This paper describes dysbalanced bioenergetic sensing owing to the failed recruitment of AMPK to the lysosomal membrane.
Shen, Y. et al. Metabolic control of the scaffold protein TKS5 in tissue-invasive, proinflammatory T cells. Nat. Immunol. 18, 1025–1034 (2017). This paper reports that T cells from patients with RA show increased tissue-invasiveness owing to the shunting of glucose towards lipogenesis and membrane formation.
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This is a summary of: Wu, B. et al. Mitochondrial aspartate regulates TNF biogenesis and autoimmune tissue inflammation. Nat. Immunol. https://doi.org/10.1038/s41590-021-01065-2 (2021)
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Mitochondrial signals regulate ER size and TNF production in rheumatoid arthritis. Nat Immunol 22, 1477–1478 (2021). https://doi.org/10.1038/s41590-021-01070-5
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DOI: https://doi.org/10.1038/s41590-021-01070-5
