Extracellular Mitochondria Research Articles

Extracellular mitochondria as mediators of dysregulation and cell death in intestinal epithelium

Extracellular mitochondria as mediators of dysregulation and cell death in intestinal epithelium

Platelets release mitochondria serving as substrate for bactericidal group IIA-secreted phospholipase A2 to promote inflammation

AbstractMitochondrial DNA (mtDNA) is a highly potent inflammatory trigger and is reportedly found outside the cells in blood in various pathologies. Platelets are abundant in blood where they promote hemostasis. Although lacking a nucleus, platelets contain functional mitochondria. On activation, platelets produce extracellular vesicles known as microparticles. We hypothesized that activated platelets could also release their mitochondria. We show that activated platelets release respiratory-competent mitochondria, both within membrane-encapsulated microparticles and as free organelles. Extracellular mitochondria are found in platelet concentrates used for transfusion and are present at higher levels in those that induced acute reactions (febrile nonhemolytic reactions, skin manifestations, and cardiovascular events) in transfused patients. We establish that the mitochondrion is an endogenous substrate of secreted phospholipase A2 IIA (sPLA2-IIA), a phospholipase otherwise specific for bacteria, likely reflecting the ancestral proteobacteria origin of mitochondria. The hydrolysis of the mitochondrial membrane by sPLA2-IIA yields inflammatory mediators (ie, lysophospholipids, fatty acids, and mtDNA) that promote leukocyte activation. Two-photon microscopy in live transfused animals revealed that extracellular mitochondria interact with neutrophils in vivo, triggering neutrophil adhesion to the endothelial wall. Our findings identify extracellular mitochondria, produced by platelets, at the midpoint of a potent mechanism leading to inflammatory responses.

Pathology and Pathogenesis of Drusen of the Optic Nervehead

This report describes the findings of a clinicopathologic correlative study of 18 cases of drusen of the optic nervehead and reports on the observations of the first ultrastructural study of this disease in the literature. From these observations, the processes of formation of drusen of the optic nervehead are proposed: abnormal axonal metabolism leads to intracellular mitochondrial calcification. Some axons rupture and mitochondria are extruded into the extracellular space. Calcium is heavily deposited in the extracellular mitochondria. Small calcified microbodies are produced and calcium continues to deposit on the surface of these nidi to form drusen. We conclude that drusen are definitely related to axonal degeneration of the optic nervehead.