You are here:
Letter to the editor: Iron, Apoptosis, and Ferroptosis
Citation:
Ghio, A. Letter to the editor: Iron, Apoptosis, and Ferroptosis. Apoptosis. Springer Nature, New York, NY, 25(1):605-606, (2020). https://doi.org/10.1007/s10495-020-01628-y
Impact/Purpose:
This letter to the editor is designed to stimulate thought as to the mechanism of apoptosis versus ferroptosis with regard to iron homeostasis.
Description:
This is a letter to the editor. A unique chemistry led to the evolutionary selection of iron for a wide range of fundamental cell functions, and the availability of this particular metal has become essential for almost every form of life. Iron concentrations in the environment were initially inadequate to meet the requirements for life and this necessitated the development of defined pathways to acquire critical metal. Concurrently, iron-catalyzed generation of radicals presented a potential for oxidative stress demanding that iron homeostasis be tightly controlled. Therefore, iron import, storage, and export are carefully regulated, and life exists at the precise interface between iron-deficiency and -sufficiency. Following an absolute iron-deficiency (e.g. anti-transferrin receptor antibodies and exposure to extracellular chelators), there is obstruction of the cell cycle at the S phase, engagement of MAP kinases, caspases, and proto-oncogene proteins, and initiation of a regulated cell death recognized as apoptosis [1]. More recently, ferroptosis regulated cell death was discovered. The definition of ferroptosis included cell death which was distinct from apoptosis, iron-dependent, and characterized by an accumulation of lipid peroxides [2]. In ferroptosis, it was suggested that accumulated iron catalyzed hydroxyl radical which, along with activation of enzymic pathways, resulted in elevated cell levels of lipid peroxides and cell denaturation. Ferroptosis was first described following cell exposure to erastin which was postulated to inhibit the cystine/glutamate antiporter leading to glutathione depletion, inactivation of glutathione peroxidase 4 (GPX4), an accumulation of lipid peroxides, and cell death [3].
