Dysfunctional mitochondria as critical players in the inflammation of autoimmune diseases: Potential role in Sjögren’s syndrome

Relevant reviews highlight the association between dysfunctional mitochondria and inflammation, but few studies address the contribution of mitochondria and mitochondria-endoplasmic reticulum (ER) contact sites (MERCs) to cellular homeostasis and inflammatory signaling. The present review outlines the important role of mitochondria in cellular homeostasis and how dysfunctional mitochondrion can release and misplace mitochondrial components (cardiolipin, mitochondrial DNA (mtDNA), and mitochondrial formylated peptides) through multiple mechanisms. These components can act as damage-associated molecular patterns (DAMPs) and induce an inflammatory response via pattern recognition receptors (PRRs). Accumulation of damaged ROS-generating mitochondria, accompanied by the release of mitochondrial DAMPs, can activate PRRs such as the NLRP3 inflammasome, TLR9, cGAS/STING, and ZBP1. This process would explain the chronic inflammation that is observed in autoimmune diseases such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), type I diabetes (T1D), and Sjögren’s syndrome.