37.1:
Overview of Cell Death
Cell death is a common process that occurs during fetal development, infection, cell damage, and aging. It can occur in a programmed or non-programmed manner.
In programmed cell death, regulated death signals lead to the killing of a specific target cell.
Apoptosis and autophagy are the two main types of programmed cell death.
Apoptosis is a highly regulated process that involves the degradation of cellular proteins by specific proteases called caspases. This results in cell shrinkage and the formation of apoptotic bodies. The apoptotic bodies are then phagocytosed by macrophages and surrounding cells.
Autophagy is a process in which various cytoplasmic components, such as old and malformed proteins and damaged organelles, accumulate inside a double-membrane vesicle known as an autophagosome. The autophagosome fuses with a lysosome forming an autolysosome where lysosomal enzymes degrade the cytoplasmic components.
Non-programmed cell death, such as necrosis, occurs when cells die accidentally due to infection, physical injury, toxins, or radiation.
Necrotic cells are characterized by swelling and disintegration of their plasma membrane and organelles, resulting in cell lysis and inflammation.
37.1:
Overview of Cell Death
Cell death is an essential process where the body gets rid of old or damaged cells. Cell proliferation and death need to be balanced, as an imbalance between the two may lead to cancer or autoimmune diseases.
Cell death was observed in the early 19th century, but there was no experimental evidence to prove it. In 1842, Carl Vogt first discovered cell death in a metamorphic toad; however, it was not termed ‘cell death.’ Scientists discovered different cell death pathways only in the 20th century with advancements in microscopy and histology.
While apoptosis, autophagy, and necrosis are the most commonly known types of death, some other types are necroptosis, pyroptosis, ferroptosis,entosis, and paraptosis. These types differ in their pathways toward cell death.
Necroptosis is a combination of apoptosis and necrosis. It begins when a ligand binds to death receptors, activating the receptor-interacting protein kinases-1 (RIPK-1) instead of caspase-8, generally activated during apoptosis. Further, many intermediate proteins are activated, causing cell swelling and lysis. Pyroptosis is a caspase-mediated cell death that involves caspase-1 or caspase-11, required for the maturation of inflammatory cytokines.
In ferroptosis, iron-dependent lipid peroxidation occurs, accumulating reactive oxygen species that eventually induce cell death. Prominent morphological features of ferroptosis include shrinkage of mitochondria and decreased cristae. During entosis, a cell gets internalized into the neighboring cell with the help of Rho GTPase and is then degraded by the lysosomal enzymes.
Paraptosis is activated when the insulin-like growth factor 1 receptor is overexpressed, triggering events leading to cell death. Paraptosis mainly occurs in neurons, and the paraptotic pathway is also being explored in apoptosis-resistant cancer cells. Anoikis is a programmed apoptotic cell death occurring in cells that get detached from the extracellular matrix. These cells follow the extrinsic or intrinsic pathways of apoptosis.