Chapter 11 - Regulated Cell Death

Abstract

Death of cells can be triggered accidentally via necrosis or in a regulated manner involving evolutionarily conserved signaling molecules and pathways. Apoptosis, the first and best characterized form of regulated cell death, plays an essential role during embryological development, following birth, and during adulthood. Apoptosis is a regulated by complex mechanisms involving a large number of molecules located in the nucleus, cytosol, ER, mitochondria, and the plasma membrane. Over the past decade, three other forms of regulated cell death have been characterized—autophagic cell death, ferroptosis, and necroptosis and pyroptosis. Autophagic cell death involves the formation of autophagosomes that transport cellular material for degradation by the lysosome resulting in the cell consuming itself from the inside. Necroptosis and pyroptosis are distinct forms of cell death that play a crucial role in protecting cells from infection by microbial pathogens. Ferroptosis results from the iron-dependent buildup of toxic lipid peroxides. In necroptosis, pyroptosis, and ferroptosis, the cell membrane ruptures resulting in the release of inflammatory proteins. Unraveling the mechanisms regulating these various modes of cell death will lead to the identification of drugs that can modulate them, which would have great value in the treatment of for a variety of serious human diseases.