Ayşe Tülay AYDINOĞLU, Evrim Aksu MENGEŞ, Burcu Balcı HAYTA

Serbest Mitokondriyal DNA’nın Sistemik Dolaşımdaki Rolü ve Hastalıkların Patogenezine Etkisi

Mitokondri, oksidatif fosforilasyon ile ATP üretiminin yanı sıra üstlendiği görevler ile hücre canlılığının sürdürülebilmesinde merkezi öneme sahip çok işlevli bir organeldir. Organelin hücre canlılığına katkıda bulunmasında rol oynayan en temel özelliklerinden biri de kendine özgül genetik sistemidir. Mitokondriyal DNA mtDNA ’nın normal fizyolojik koşullarda organelin matriks kısmında bulunduğu, fakat gerek organel gerekse hücre hasarı olduğu durumda hücre dışı matrise salınarak serbest dolaşıma katıldığı belirtilmiştir. Özellikle son yıllarda mtDNA’ya ilişkin yapılan çalışmalar, organel genomunun dolaşımda üstlendiği roller ve hastalıklarla ilişkisi üzerine yoğunlaşmıştır. Sistemik dolaşımda serbest halde bulunan mtDNA’lar [circulating cell free mtDNA ccf-mtDNA ] bağışıklık sisteminde görevli Kalıp Tanıma Reseptörleri [Pattern Recognition Receptors PRRs ] tarafından Hasarla İlişkili Moleküler Yapılar [Damage Associated Molecular Patterns DAMPs ] olarak algılanarak pro-inflamatuar yanıt oluşumunda temel bir rol üstlenmektedir. Bu derlemede, ccf-mtDNA’nın sistemik dolaşıma katılma mekanizmaları ve etkileşimde bulunduğu yolakların detayına inilerek, bağışıklık sisteminin bir uyaranı olarak görev almasına ve hastalıklarla ilişkisine dair bilgiler özetlenmiştir

The Role of Circulating Cell-Free Mitochondrial Dna In Systemic Circulation and Its Effect On Diseases Pathogenesis

Mitochondria are multi-functional organelles with many essential roles in the maintenance of cell viability as well as ATP production by oxidative phosphorylation. One of the most important features of this organelle that contributes to cell viability is its own genetic system. Mitochondrial DNA mtDNA , which is located in the mitochondrial matrix under normal physiological conditions, is released into the extracellular matrix and enters the systemic circulation in case of an organelle and/or a cellular damage. Recent studies have focused on the role of mtDNA in circulation and its association with diseases. Circulating cell-free mtDNA ccf-mtDNA is regarded as a Damage Associated Molecular Pattern DAMP and recognised by the Pattern Recognition Receptors PRRs . They play a fundamental role in initiating the pro-inflammatory response. In this review, the mechanisms of ccf-mtDNA-induced inflammatory pathways in systemic circulation and the effect of ccf-mtDNA on diseases pathogenesis will be discussed

Keywords:

ccf-mtDNA, systemic circulation, inflammation,

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