Heme induced cell death: You can run from TLR4 but you cannot hide from ROS

Heme is the prosthetic group of several enzymes and proteins, including cytochrome c oxidase and hemoglobin. During hemolytic events, high amounts of heme derived from hemoglobin can be released from red blood cells, contributing to the pathogenesis of different hemolytic diseases. Heme-induced cell death is an important player in this situation, and different studies report that heme stimulus can lead to distinct types of regulated cell death. Here, I hypothesize that, when incubated in the presence of high heme concentration, macrophages display concomitant and distinct types of cell death, including necroptosis and a yet to be identified type of cell death. This hypothesis is based on recently published results discussed throughout this manuscript.