Mechanisms and pathophysiological significance of eryptosis, the suicidal erythrocyte death

• Upon injury, circulating erythrocytes may enter suicidal cell death or eryptosis.
• Most important triggers of eryptosis include enhanced cytosolic Ca2+ activity and ceramide.
• Regulation of eryptosis involves AMPK, GK, PAK2, CK1α, JAK3, PKC, p38-MAPK.
• Diseases with enhanced eryptosis include genetic disorders, sepsis, malaria, renal failure and hyperbilirubinemia.
• Excessive eryptosis may lead to anemia and impaired microcirculation.

Eryptosis, the suicidal erythrocyte death characterized by cell shrinkage and cell membrane scrambling, is stimulated by Ca2+ entry through Ca2+-permeable, PGE2-activated cation channels, by ceramide, caspases, calpain, complement, hyperosmotic shock, energy depletion, oxidative stress, and deranged activity of several kinases (e.g. AMPK, GK, PAK2, CK1α, JAK3, PKC, p38-MAPK). Eryptosis is triggered by intoxication, malignancy, hepatic failure, diabetes, chronic renal insufficiency, hemolytic uremic syndrome, dehydration, phosphate depletion, fever, sepsis, mycoplasma infection, malaria, iron deficiency, sickle cell anemia, thalassemia, glucose 6-phosphate dehydrogenase deficiency, and Wilson's disease. Eryptosis may precede and protect against hemolysis but by the same token result in anemia and deranged microcirculation.