The following is a summary of the “Heme-dependent induction of mitophagy program during differentiation of murine erythroid cells,” published in the February 2023 issue of Hematology by Ikeda, et al.
The huge production of heme in erythroblasts requires the development and maintenance of mitochondria, which in turn requires the degradation of mitochondria upon terminal differentiation to red blood cells (RBCs), generating a biphasic regulation process. Recent work by their group showed that mitochondrial retention in RBCs is increased by iron deprivation in mice, which suggests that iron and/or heme are required for the destruction of mitochondria during erythroblast maturation.
They analysed the expression of genes associated with GATA1 and autophagy and the effect of iron or heme restriction on the number of mitochondria to learn more about the interaction between iron or heme and mitophagy. According to their findings, heme stimulates the activation of mitophagy and the expression of GATA1-regulated genes involved in mitophagy.
In murine erythroleukemia (MEL) cells and a genetic rescue system with G1E-ER-GATA1 erythroblast cells produced from Gata1-null murine embryonic stem cells, GATA1 may increase the expression of the autophagy-related genes Atg4d and Stk11 for mitophagy via a heme-dependent mechanism. Their findings support a 2 step mechanism in which mitochondria play a crucial role in heme production, and where the heme produced during differentiation promotes mitophagy and the disposal of mitochondria. By elucidating the molecular underpinnings of this process, this method sheds light on a crucial step in cell biology.
Source: sciencedirect.com/science/article/abs/pii/S0301472X22008116
