Danger signals from mitochondrial DAMPS in trauma and post-injury sepsis
In all multicellular organisms, immediate host responses to both sterile and infective threat are initiated by very primitive systems now grouped together under the general term ‘danger responses’. Danger signals are generated when primitive ‘pattern recognition receptors’ (PRR) encounter activating ‘alarmins’. These molecular species may be of pathogenic infective origin (pathogen-associated molecular patterns) or of sterile endogenous origin (danger-associated molecular patterns). There are many sterile and infective alarmins and there is considerable overlap in their ability to activate PRR, but in all cases the end result is inflammation. It is the overlap between sterile and infective signals acting via a relatively limited number of PRR that generally underlies the great clinical similarity we see between sterile and infective systemic inflammatory responses. Mitochondria (MT) are evolutionarily derived from bacteria, and thus they sit at the crossroads between sterile and infective danger signal pathways. Many of the molecular species in mitochondria are alarmins, and so the release of MT from injured cells results in a wide variety of inflammatory events. This paper discusses the known participation of MT in inflammation and reviews what is known about how the major.
Funded by the United States Department of Defense focused program award W81XWH-16-1-0464.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no relevant conflicts of interest.
- 2.Moore FA, Moore EE, Poggetti R, et al. Gut bacterial translocation via the portal vein: a clinical perspective with major torso trauma. J Trauma. 1991;31:629–36 (discussion 636–8).Google Scholar
- 6.Bone RC. Toward an epidemiology and natural history of SIRS (systemic inflammatory response syndrome). JAMA;268:3452–5.Google Scholar
- 20.Kaczmarek E, Hauser CJ, Kwon WY, Rica I, Chen L, Sandler N, Otterbein LE, Campbell Y, Cook CH, Yaffe MB, Marusich M, Itagaki K. A subset of five human Mitochondrial formyl peptides mimics bacterial peptides and functionally deactivates human neutrophils. J Trauma Acute Care Surg. https://doi.org/10.1097/TA.0000000000001971 (in press).
- 21.Dosch M, Gerber J, Jebbawi F, et al. Mechanisms of ATP release by inflammatory cells. Int J Mol Sci. https://doi.org/10.3390/ijms19041222 (19. Epub Ahead of Print April 18, 2018).
- 36.Safdar A, Tarnopolsky MA. Exosomes as mediators of the systemic adaptations to endurance exercise. Cold Spring Harb Perspect Med. https://doi.org/10.1101/cshperspect.a029827 (8. Epub ahead of print March 1, 2018).
- 39.Rodriguez A-M, Nakhle J, Griessinger E, et al. Intercellular mitochondria trafficking highlighting the dual role of mesenchymal stem cells as both sensors and rescuers of tissue injury. Cell Cycle. 2018;1–25.Google Scholar
- 41.Berridge MV, Herst PM, Rowe MR, et al. Mitochondrial transfer between cells: Methodological constraints in cell culture and animal models. Anal Biochem. https://doi.org/10.1016/j.ab.2017.11.008 (Epub ahead of print November 21, 2017).