Apoptosis and Cell Death

Abstract

Cell death plays a central role in multicellular organisms during their early development in sculpting the body parts and in their adult life by controlling cell numbers (homeostasis), and cell death further protects the organism overall by removing all cells damaged by disease, aging, infection, genetic mutation, and exposure to toxic agents. Kerr et al1 coined the term “apoptosis,” referring to a particular morphology of physiological cell death involving cell shrinkage, nuclear condensation, membrane blebbing, and cellular and nuclear fragmentation into membrane-bound apoptotic bodies (Fig. 4.1). The lipid changes that occur in the membrane eventually lead to phagocytosis of the apoptotic cellular fragments. Often apoptosis is used synonymously with programmed cell death, implying that death results from the regulated activation of a preexisting death program that is encoded in the genome. The first evidence of a genetic program that orchestrates physiological cell death came from the developmental studies of the nematode Caenorhabditis elegans. 2 Our knowledge of cell death and the mechanisms of its regulation increased dramatically in the past two decades with the discovery of several death genes in C. elegans 3 and their counterparts in mammals. Now it is clear that apoptotic cell death has important biological roles not only in development and homeostasis but also in the pathogenesis of several disease processes. Dysregulation of apoptosis is found in a wide spectrum of human diseases, including cancer, autoimmune diseases, neurodegenerative diseases, ischemic diseases, and viral infections.4 Interestingly, death programs other than apoptosis with different morphological features were also considered in controlling the cell numbers. These death programs could be directed by the condemned cell itself or by neighboring cells, with or without the help of humoral factors.