Mechanisms of microparticle generation: on the trail of the mitochondrion!

Semin Thromb Hemost. 2010 Nov;36(8):833-44. doi: 10.1055/s-0030-1267037. Epub 2010 Nov 3.

Abstract

Membrane remodeling, phosphatidylserine (PS) exposure, and subsequent microparticle (MP) shedding regulation is a critical step in maintaining vascular homeostasis. Shed MP, more particularly those of platelet origin, could be viewed as a way to increase the catalytic procoagulant surface relying on the essential presence of PS for optimal hemostatic response. Whether "flip-flop" is mandatory for the release of MP is suggested from the phenotype of Scott's syndrome, a rare bleeding disorder in which both PS exposure and MP shedding are deficient. PS exposure results from a specific cytoskeleton degradation pathway involving caspases, tuned by mitochondria permeability changes, and requiring a sustained increase in intracellular calcium. The actual roles of transmembrane ion transport or transient transmembrane pores in PS exposure remain to be more firmly established. Considering that an excess of plasma membrane procoagulant activity is associated with an increased risk of thrombosis, the identification of effectors of PS exposure and MP release appear relevant targets in thrombosis research and focused drug design. In this view, animal models of Scott's syndrome should prove of primary importance for the characterization of the genetic trait(s) accounting for the associated defect that would provide an important hint toward the control of PS exposure and subsequent MP release.

Publication types

  • Review

MeSH terms

  • Animals
  • Blood Coagulation Disorders / etiology
  • Cell-Derived Microparticles / metabolism*
  • Homeostasis
  • Humans
  • Mitochondria / metabolism*
  • Phosphatidylserines / metabolism*
  • Phosphatidylserines / physiology

Substances

  • Phosphatidylserines