Abstract
Erythrocytes are among the most abundant cells in mammals and are perfectly adapted to their main functions, i.e., the transport of O2 to peripheral tissues and the contribution to CO2 transport to the lungs. In contrast to other cells, they are fully devoid of organelles. Similar to apoptosis of nucleated cells erythrocytes may enter suicidal death, eryptosis, which is characterized by the presentation of membrane phosphatidylserine on the cell surface and cell shrinkage, hallmarks that are also typical of apoptosis. Eryptosis may be triggered by an increase in the cytosolic Ca2+ concentration, which may be due to Ca2+ influx via non-selective cation channels of the TRPC family. Eryptosis is further induced by ceramide, which sensitizes erythrocytes to the eryptotic effect of Ca2+. Signaling regulating eryptosis further involves a variety of kinases including AMPK, PAK2, cGKI, JAK3, CK1α, CDK4, MSK1/2 and casein kinase. Eryptosis-dependent shrinkage is induced by K+ efflux through Ca2+-activated K+ channel KCa3.1, the Gardos channel. Eryptotic cells are phagocytosed and may adhere to endothelial cells. Eryptosis may help prevent hemolysis since defective erythrocytes usually undergo eryptosis followed by rapid clearance from circulating blood. Excessive eryptosis stimulated by various diseases and xenobiotics may result in anemia and/or impaired microcirculation. This review focuses on the significance and mechanisms of eryptosis as well as on the ion fluxes involved. Moreover, a short summary of further ion transport mechanisms of the erythrocyte membrane is provided.
Highlights
The number of erythrocytes or red blood cells (RBCs) exceeds the numbers of most other cells in the human body and amounts to 4–6 × 106 per μl of blood (Nemkov et al, 2018)
It has become clear that erythrocytes, the lifespan of which has a median of 120 days in human beings, can actively undergo a controlled suicidal death program which is in many aspects comparable to apoptosis of nucleated cells (Föller et al, 2008b; Lang et al, 2008). It has been called eryptosis and is mainly characterized by two hallmarks that are typical of apoptosis (Repsold and Joubert, 2018): The externalization of membrane phosphatidylserine at the cell surface and the loss of cell volume, i.e., cell shrinkage (Föller et al, 2008b; Lang et al, 2008)
We use the term “eryptosis” in this review because we believe that it well reflects the similarities to apoptosis of nucleated cells and at the same time points to the obvious limitations associated with erythrocytes being cells without organelles
Summary
The number of erythrocytes or red blood cells (RBCs) exceeds the numbers of most other cells in the human body and amounts to 4–6 × 106 per μl of blood (Nemkov et al, 2018). It allows cells to die in a controlled sequence of events that affect the cytosol and different organelles It comprises the breakdown of the mitochondrial potential, karyopyknosis (shrinkage of the nucleus and chromatin condensation) with subsequent DNA degradation, Ca2+ influx and Ca2+-dependent enzymatic digestion of intracellular proteins as well as breakdown of the phosphatidylserine asymmetry of the cell membrane (Guo et al, 2009; D’Arcy, 2019). We use the term “eryptosis” in this review because we believe that it well reflects the similarities to apoptosis of nucleated cells and at the same time points to the obvious limitations associated with erythrocytes being cells without organelles
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