[Genetic and molecular insights into apoptosis]

Abstract

Apoptosis, or programmed cell death, is a crucial mechanism for the survival of organisms and is functionally conserved in all higher eukaryotes. Molecular events in apoptosis are responsible for removal of damaged or infected cells from the cellular population, which links apoptosis to the cell cycle, replication and DNA repair. Moreover, apoptosis is one of the main mechanisms governing accurate embryonic development and maintenance of tissue homeostasis. In the invertebrate species Drosophila melanogaster and Caenorhabditis (C.) elegans apoptotic mechanisms are relatively simple, whereas in vertebrates they become more complex and include large groups of molecular components. There are two distinct apoptotic pathways in mammals. The first is called the "death receptor pathway" and is initiated by extracellular ligands such as TNFalpha, or FasL (Fas ligand)/CD95L, TWEAK and TRAIL. They bind to their receptors on the cellular surface, i.e., TNFR, Fas/CD95, DR3, DR4/DR5. The second pathway that also leads to the caspase activation is under the control of the Bcl-2 family of genes and proteins. Although C. elegans has only two members of Bcl-2 family, CED-9 and EGL-1, higher eukaryotes possess 30 homologs of this protein family. They can be categorized as those that promote cellular survival and those that exert proapoptotic action and induce programmed cell death. The final result of both apoptotic signaling pathways is the activation of cellular caspase. When considering a broader picture of apoptosis, these biological phenomena can today be interpreted in the new light as a basic mechanism of an organism life preserving.