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The source of cell-free mitochondrial DNA in trauma and potential therapeutic strategies
Kabilan Thurairajah1, Gabrielle Daisy Briggs1, Zsolt Janos Balogh2
1Department of Traumatology, John Hunter Hospital and University of Newcastle, Newcastle, NSW, Australia.
Abstract:
Mitochondria play a key role in the pathophysiology of post-injury inflammation. Cell-free mitochondrial DNA (cf-mtDNA) is now understood to catalyse sterile inflammation after trauma. Observations in trauma cohorts have identified high cf-mtDNA in patients with systemic inflammatory response syndrome and multiple organ failure as well as following major surgery. The source of cf-mtDNA can be various cells affected by mechanical and hypoxic injury (passive mechanism) or induced by inflammatory mechanisms (active mechanism). Multiple forms of cf-mtDNA exist; mtDNA fragments, mtDNA in microparticles/vesicles and cell-free mitochondria. Trauma to cells that are rich in mitochondria are believed to release more cf-mtDNA. This review describes the current understanding of the mechanisms of cf-mtDNA release, its systemic effects and the potential therapeutic implications related to its modification. Although current understanding is insufficient to change trauma management, focussed research goals have been identified to pave the way for monitoring and manipulation of cf-mtDNA release and effects in trauma.
Insights
Cell-free mitochondrial DNA (cf-mtDNA) drives sterile inflammation post-trauma. Understanding cf-mtDNA release mechanisms and effects is crucial for future trauma management strategies.
Area of Science:
- Biomedical Science
- Trauma Pathophysiology
- Immunology
Background:
- Mitochondria are central to post-injury inflammation.
- Cell-free mitochondrial DNA (cf-mtDNA) catalyzes sterile inflammation after trauma.
- Elevated cf-mtDNA is observed in trauma patients with systemic inflammatory response syndrome and multiple organ failure.
Purpose of the Study:
- To review the current understanding of cf-mtDNA release mechanisms post-trauma.
- To describe the systemic effects of cf-mtDNA.
- To explore potential therapeutic implications for modifying cf-mtDNA in trauma.
Main Methods:
- Literature review of current research on cf-mtDNA in trauma.
- Analysis of observations in trauma cohorts.
- Discussion of proposed mechanisms for cf-mtDNA release (passive and active).
Main Results:
- cf-mtDNA is released through passive (mechanical/hypoxic injury) and active (inflammatory) mechanisms.
- Various forms of cf-mtDNA exist, including fragments, microparticles, and cell-free mitochondria.
- Cells rich in mitochondria are significant sources of cf-mtDNA release.
Conclusions:
- Current understanding of cf-mtDNA is insufficient to alter trauma management.
- Focused research is needed to monitor and manipulate cf-mtDNA release and its effects.
- Future research aims to develop therapeutic strategies targeting cf-mtDNA in trauma care.
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