Role of Mitochondrial Permeability Transition Pore in Coated-Platelet Formation

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Abstract
Objective— Coated-platelets are a subset of cells observed during costimulation of platelets with collagen and thrombin. Important characteristics of coated-platelets include retention of multiple α-granule proteins and expression of phosphatidylserine on the cell surface. The mitochondrial permeability transition pore (MPTP) is a key step in apoptosis and is suggested to be involved in some forms of platelet activation. The objective of this study was to examine the role of MPTP in the synthesis of coated-platelets. Methods and Results— Flow cytometric analysis of coated-platelet production was used to examine the impact of pharmacological effectors of MPTP formation. Cyclosporin A, coenzyme Q, and bongkrekic acid all inhibit MPTP formation as well as production of coated-platelets. Phenylarsine oxide and diamide, both potentiators of MPTP formation, stimulate coated-platelet synthesis. Atractyloside, another inducer of MPTP formation, does not affect the percentage of coated-platelets synthesized; however, it does increase the level of phosphatidylserine exposed on the surface of coated-platelets. Conclusions— These findings indicate that MPTP formation is an integral event in the synthesis of coated-platelets. Although the exact function of the MPTP remains to be determined, these data support a growing body of evidence that apoptosis-associated events are vital components of the platelet activation process. Formation of coated-platelets involves a complex set of activation events initiated by dual agonist activation. The mitochondrial permeability transition pore (MPTP) is a key intermediate in apoptosis and has been suggested to impact platelet activation. This report demonstrates that MPTP formation is essential to production of coated-platelets.