The platelet-mitochondria nexus in autoimmune and musculoskeletal diseases

• Published in: Clinical immunology (Orlando, Fla.) Fla.), 2024-10, Vol.267, p.110350, Article 110350
• Main Authors: Michailidou, Despina, Giaglis, Stavros, Dale, George L.
• Format: Article
• Language: English
• Subjects: Autoimmune diseases; Mitochondria; Musculoskeletal diseases; Platelets
• ISSN: 1521-6616; 1521-7035; 1521-7035
• DOI: 10.1016/j.clim.2024.110350

Platelets are crucial for thrombosis and hemostasis. Importantly, they contain mitochondria that are responsible for energy generation and therefore vital for platelet survival and activation. Activated platelets can release mitochondria that may be free or encapsulated in platelet extracellular vesicles (EVs). Extruded mitochondria are a well-known source of mitochondrial DNA, and mitochondrial antigens that can be targeted by autoantibodies forming immune complexes (IC). Interaction of IC with the platelet cell surface FcγRIIA receptor results in platelet activation and release of platelet granule components. In this review, we summarize how platelets and mitochondria may contribute to the pathogenesis of different autoimmune and musculoskeletal diseases. Targeting key drivers of mitochondrial extrusion may ultimately lead to urgently needed targeted pharmacological interventions for treating inflammation and thrombotic diathesis, and halting organ damage in some of these rheumatological conditions. •Platelets not only play a crucial role in hemostasis and clotting but are participants in both adaptive and innate immune responses.•Activated platelets can extrude either free mitochondria or encapsulated in platelet microparticles.•Extracellular mitochondria are a source of mitochondrial DNA and antigens that can be targeted by autoantibodies forming immune complexes•Mitochondria released from activated platelets may partake in the pathogenesis of several autoimmune and musculoskeletal diseases.•Targeting platelet mediated mitochondrial extrusion may prevent inflammation in autoimmune and musculoskeletal diseases.