"Iron"ing out hemophagocytosis through PIEZO1

Abstract

In this issue of Cell, Ma et al. reveal a mechanistic role for PIEZO1 in iron homeostasis through molecular genetic mouse studies. They also demonstrate implications for human iron overload and deficiency syndromes, susceptibility to malarial infection, and red blood cell turnover in persons of African ancestries.

Figure 1.. Putative roles of PIEZO1 in iron homeostatis and human health

In mice (left panel), PIEZO1 activation leads to intracellular flux of calcium and hemophagocytosis of red blood cells. This in turn regulates levels of intermediates of red cell breakdown and iron uptake in the liver as part of iron homeostasis. Gain of function (GOF) of Piezo1 leads to increased serum iron and accumulation of liver iron stores. In humans (right panel), a PIEZO1 GOF allele (E756del) is associated with both resistance to malaria and increased serum iron markers and is common among populations of West African ancestry (https://popgen.uchicago.edu/ggv/). The yellow portion of each circle represents the frequency of the ancestral allele in the overlapped countries; the blue sector represents the derived E756del allele.