Diversity and complexity of cell death: a historical review

Death is the inevitable fate of all living organisms, whether at the individual or cellular level. For a long time, cell death was believed to be an undesirable but unavoidable final outcome of nonfunctioning cells, as inflammation was inevitably triggered in response to damage. However, experimental evidence accumulated over the past few decades has revealed different types of cell death that are genetically programmed to eliminate unnecessary or severely damaged cells that may damage surrounding tissues. Several types of cell death, including apoptosis, necrosis, autophagic cell death, and lysosomal cell death, which are classified as programmed cell death, and pyroptosis, necroptosis, and NETosis, which are classified as inflammatory cell death, have been described over the years. Recently, several novel forms of cell death, namely, mitoptosis, paraptosis, immunogenic cell death, entosis, methuosis, parthanatos, ferroptosis, autosis, alkaliptosis, oxeiptosis, cuproptosis, and erebosis, have been discovered and advanced our understanding of cell death and its complexity. In this review, we provide a historical overview of the discovery and characterization of different forms of cell death and highlight their diversity and complexity. We also briefly discuss the regulatory mechanisms underlying each type of cell death and the implications of cell death in various physiological and pathological contexts. This review provides a comprehensive understanding of different mechanisms of cell death that can be leveraged to develop novel therapeutic strategies for various diseases. Cell death is a complex and interconnected process that plays a crucial role in maintaining tissue homeostasis and preventing disease. There are various types of cell death, including necrosis, apoptosis, autophagy, and others, each with distinct morphological features and molecular mechanisms. Understanding the diverse processes underlying cell death is essential for understanding diseases and developing new therapies. Recent research has focused on characterizing and distinguishing various forms of cell death, thereby advancing our understanding of their roles in health and disease. The complex mechanisms underlying cell death are underscored by the intricate interconnections among different types of cell death and the regulation of these mechanisms through diverse signaling pathways and environmental factors. Further research is necessary to fully characterize and differentiate among the various forms of cell death and their roles in pathological conditions.