Mitochondria at the Crossroads: Unveiling the Link Between Sjögren’s Syndrome and Mitochondrial Dysfunction
Mitochondria at the Crossroads: Unveiling the Link Between Sjögren’s Syndrome and Mitochondrial Dysfunction
Ali Bejani,1Majid Sadeghpour,2Nasrin Moghimi,3,*
1. Student Research Committee, Kurdistan University of Medical Sciences, Sanandaj, Iran 2. Department of General Medicine, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran 3. Cancer & Immunology Research Center, Research Institute for Health Development, Kurdistan University of Medical Sciences, Sanandaj, Iran.
Introduction: Sjögren’s Syndrome (SS) is a chronic autoimmune disorder primarily characterized by the destruction of exocrine glands, leading to symptoms such as dry mouth and eyes. Despite significant research, the precise mechanisms driving this glandular dysfunction remain unclear. Emerging evidence suggests a potential link between mitochondrial dysfunction and the pathogenesis of autoimmune diseases, including SS.
Methods: A comprehensive review of the literature was conducted, focusing on clinical observations, molecular studies, and experimental data that investigate mitochondrial involvement in SS. The review also examines how mitochondrial dysfunction can influence key pathological processes, such as oxidative stress, apoptosis, and immune responses
Results: The review reveals that mitochondrial dysfunction plays a critical role in the pathophysiology of SS. Mitochondrial abnormalities, such as impaired oxidative phosphorylation and increased production of reactive oxygen species, lead to significant cellular damage and energy deficits in exocrine glands. That is why the administration of antioxidants may be effective in the prevention and treatment of this syndrome. This dysfunction exacerbates oxidative stress, promoting chronic inflammation and contributing to the glandular destruction characteristic of SS. Additionally, mitochondrial-mediated apoptosis and the release of mitochondrial DNA act as triggers for sustained immune responses, furthering tissue damage and autoimmune activity.
Moreover, mitochondrial dysfunction impacts immune cell behavior, particularly in T cells and macrophages, driving a pro-inflammatory phenotype that worsens the autoimmune response in SS. This dysfunction is also implicated in the formation of ectopic lymphoid structures within the salivary glands, which are associated with severe disease and increased autoantibody production. These findings suggest that mitochondrial dysfunction is a driving factor in SS pathogenesis, highlighting the potential for novel therapeutic strategies targeting mitochondrial health to slow disease progression and improve patient outcomes.
Conclusion: Understanding the role of mitochondrial dysfunction in SS opens new avenues for therapeutic intervention. Targeting mitochondrial health through antioxidants, mitochondrial biogenesis enhancers, and personalized medicine approaches based on mitochondrial biomarkers could offer promising strategies for managing this debilitating disease. Further research is needed to fully elucidate the complex interplay between mitochondria and autoimmune processes in SS, which could lead to more effective treatments and improved patient outcomes.