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Abstract
Mitochondrial oxidative stress activates protective mitophagy in autoimmune thyroiditis.
- Mitochondrial reactive oxygen species (mtROS) activate signaling pathways involving ATM and CHEK2 in thyroid epithelial cells.
- CHEK2 phosphorylates TAX1BP1, enhancing its ability to bind to specific ubiquitin chains, which promotes the removal of damaged mitochondria.
- Impairment of mitophagy through a mutated form of TAX1BP1 leads to increased levels of cytosolic mitochondrial DNA and heightened activity of the STING1 pathway.
- Loss of either Pink1 or Prkn exacerbates thyroiditis in mouse models, indicating their role in disease progression.
- Inhibition of STING1 with C-176 decreases inflammation and thyroid autoantibody responses in knockout models.
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