When Our Best Friend Becomes Our Worst Enemy: The Mitochondrion in Trauma, Surgery, and Critical Illness

Area of Science:

• Immunology
• Critical Care Medicine
• Cell Biology

Background:

• Tissue injury triggers systemic inflammation via damage-associated molecular patterns (DAMPs).
• Mitochondria, originating from bacteria, release similar molecular patterns (mDAMPs) upon cell death.
• These mDAMPs can activate the innate immune system, contributing to organ-wide damage.

Purpose of the Study:

• To review the role of mitochondrial DAMPs (mDAMPs) in critical illness.
• To discuss the function, release, targets, and inflammatory potential of various mDAMPs.
• To highlight the knowledge gaps in understanding and counteracting mDAMPs in patients.

Main Methods:

• Literature review of mDAMPs in major surgery, trauma, sepsis, and critical care.
• Discussion of specific mDAMPs including mitochondrial DNA, cardiolipin, and cytochrome C.
• Analysis of mDAMPs' presence in circulation, free or within extracellular vesicles.

Main Results:

• mDAMPs are released from damaged mitochondria into extracellular spaces and circulation.
• mDAMPs activate innate immunity, contributing to inflammation in critical illness.
• Specific mDAMPs identified include mitochondrial DNA, cardiolipin, N-formyl peptides, cytochrome C, ATP, ROS, succinate, and mitochondrial transcription factor A.

Conclusions:

• The precise role of mDAMPs in trauma, sepsis, and critical care requires further elucidation.
• There is a significant lack of knowledge regarding therapeutic strategies to counteract mDAMPs in patients.
• Further research into mDAMPs is essential for advancing critical care and trauma management.