# Eryptosis: Programmed Death of Nucleus-Free, Iron-Filled Blood Cells

## TL;DR

This paper explores eryptosis, the programmed death of red blood cells, and its role in health and disease.

## Contribution

The paper provides a detailed overview of the mechanisms and consequences of eryptosis, linking it to ferroptosis and disease.

## Key findings

- Eryptosis involves pathways like Ca2+ influx, ceramide generation, and oxidative stress.
- Dysregulated eryptosis is linked to infectious diseases and hematologic disorders.
- Eryptosis shares similarities with ferroptosis in iron-dependent cell death.

## Abstract

Human erythrocytes are organelle-free cells packaged with iron-containing hemoglobin, specializing in the transport of oxygen. With a total number of approximately 25 trillion cells per individual, the erythrocyte is the most abundant cell type not only in blood but in the whole organism. Despite their low complexity and their inability to transcriptionally upregulate antioxidant defense mechanisms, they display a relatively long life time, of 120 days. This ensures the maintenance of tissue homeostasis where the clearance of old or damaged erythrocytes is kept in balance with erythropoiesis. Whereas the regulatory mechanisms of erythropoiesis have been elucidated over decades of intensive research, the understanding of the mechanisms of erythrocyte clearance still requires some refinement. Here, we present the main pathways leading to eryptosis, the programmed death of erythrocytes, with special emphasis on Ca2+ influx, the generation of ceramide, oxidative stress, kinase activation, and iron metabolism. We also compare stress-induced erythrocyte death with erythrocyte ageing and clearance, and discuss the similarities between eryptosis and ferroptosis, the iron-dependent regulated death of nucleated blood cells. Finally, we focus on the pathologic consequences of deranged eryptosis, and discuss eryptosis in the context of different infectious diseases, e.g., viral or parasitic infections, and hematologic disorders.