Apoptosis, often referred to as programmed cell death, is a fundamental biological process that plays a crucial role in maintaining the balance and health of multicellular organisms. It was first observed over a century ago, but its significance and underlying mechanisms have only been unraveled in recent decades. This article will explore the journey of its discovery and delve into the fascinating mechanisms behind cellular apoptosis.
The term "apoptosis" was coined in 1972 by John Kerr, Andrew Wyllie, and Alastair Currie to describe a morphologically distinct form of cell death, different from the already known necrosis. However, it wasn't until the 1980s, with studies on the nematode Caenorhabditis elegans, that the true significance of apoptosis began to be understood.
Researchers led by Robert Horvitz identified specific genes responsible for programmed cell death in C. elegans. They found that mutations in these genes resulted in an increased number of cells due to a failure of programmed cell death. This work, which earned Horvitz the Nobel Prize in Physiology or Medicine in 2002, paved the way for understanding the molecular mechanisms of apoptosis.
Apoptosis can be triggered by various stimuli, both internal and external, and involves a complex cascade of biochemical events. There are two primary pathways for apoptosis – the intrinsic (mitochondrial) pathway and the extrinsic (death receptor) pathway.
Intrinsic Pathway: This pathway is triggered by internal stimuli such as DNA damage, oxidative stress, or deprivation of growth factors. It involves the permeabilization of the mitochondrial outer membrane, leading to the release of cytochrome c. Cytochrome c then binds to a protein called Apaf-1, forming a complex known as the apoptosome, which activates a class of proteins known as caspases that carry out the cell death process.
Extrinsic Pathway: This pathway is initiated by the binding of external ligands to death receptors on the cell surface. This binding triggers the recruitment of adaptor proteins and the formation of the death-inducing signaling complex (DISC), which also leads to the activation of caspases.
Both pathways ultimately result in the activation of effector caspases (such as caspase-3 and caspase-7), which go on to dismantle the cell. They cleave key cellular proteins, leading to the characteristic morphological changes of apoptosis, including cell shrinkage, chromatin condensation, and formation of apoptotic bodies.