<> "The repository administrator has not yet configured an RDF license."^^ . <> . . "Mitochondrial Signatures in Extracellular Vesicles:A Link Between Autoimmunity and Aging"^^ . "Autoimmune diseases and aging share common phenotypic features, including immune cell dysregulation and mitochondrial dysfunction. In recent years, mitochondria have emerged as key regulators of immune cell function. While mitochondria can affect cell metabolism, their regulatory function is not limited to the intracellular space. The transfer of mitochondrial cargo between two cells can alter recipient cell function and phenotype. \r\nSeveral mechanisms of mitochondrial transfer have been demonstrated, one of which utilizes the release of extracellular vesicles (EVs) carrying mitochondrial cargo in the form of mitochondrial protein or mitochondrial DNA (mtDNA), termed MitoEVs. EVs are biologically active particles produced by most cells in the human body and can cross the blood-brain barrier. Due to their ubiquitous origin and diverse cargo, EVs have been utilized as diagnostic and prognostic biomarkers and have been shown to participate in several physiological and pathological processes. \r\nThis dissertation explores mitochondrial cargo as a component of a shared EV signature in autoimmunity and aging, with the goal of identifying MitoEV-producer cells. To enable this research, I established an optimized isolation protocol that achieved high yields and purity of EVs while minimizing contamination from co-isolated particles, such as platelets and lipoproteins. This protocol provided the foundation for downstream mitochondrial cargo analysis in both large and small EVs.\r\nUsing cellular models, I demonstrated that the production of MitoEVs results in the release of EVs with distinct molecular profiles depending on the induction mode. In Jurkat cells treated with either ionizing irradiation or lysosomal inhibition, irradiation increased mutated mtDNA cargo primarily in small EVs. In contrast, lysosomal inhibition triggered the release of mitochondrial proteins in large EVs.\r\nTo understand MitoEVs in autoimmunity and aging, I analyzed small and large EVs isolated from systemic lupus erythematosus (SLE) and multiple sclerosis (MS) patients and from young (20-25 years) and old (60-70 years) healthy donors. Proteomic analysis revealed that mitochondrial proteins are enriched in EVs derived from SLE patients and old individuals, although this enrichment is not present across autoimmune diseases. Furthermore, MitoEVs from older donors carried mtDNA with increased levels of low-frequency mutations, consistent with the stochastic accumulation of mutations during aging in cells. Finally, I demonstrated that mtDNA mutations in EVs and PBMCs can be leveraged to trace EVs back to their producer cells.\r\nMy work highlights mitochondrial cargo in EVs as a molecular link between autoimmunity and aging, laying the foundation for future research on the modulatory roles of MitoEVs in these conditions."^^ . "2026" . . . . . . . "Iris"^^ . "Potakowskyj"^^ . "Iris Potakowskyj"^^ . . . . . . "Mitochondrial Signatures in Extracellular Vesicles:A Link Between Autoimmunity and Aging (PDF)"^^ . . . "Mitochondrial Signatures in Extracellular Vesicles:A Link Between Autoimmunity and Aging (Other)"^^ . . . . . . "Mitochondrial Signatures in Extracellular Vesicles:A Link Between Autoimmunity and Aging (Other)"^^ . . . . . . "Mitochondrial Signatures in Extracellular Vesicles:A Link Between Autoimmunity and Aging (Other)"^^ . . . . . . "Mitochondrial Signatures in Extracellular Vesicles:A Link Between Autoimmunity and Aging (Other)"^^ . . . . . . "Mitochondrial Signatures in Extracellular Vesicles:A Link Between Autoimmunity and Aging (Other)"^^ . . . . . "HTML Summary of #36781 \n\nMitochondrial Signatures in Extracellular Vesicles:A Link Between Autoimmunity and Aging\n\n" . "text/html" . . . "570 Biowissenschaften, Biologie"@de . "570 Life sciences"@en . .