celldeath

Cell death refers to the end of a cell's life, a fundamental biological process that shapes development, tissue homeostasis, and responses to stress. It encompasses both regulated, programmed processes and accidental, traumatic loss. Major forms include apoptosis, necrosis, and autophagy-related mechanisms, as well as regulated necrosis such as necroptosis, pyroptosis, and ferroptosis. The specific mode of death influences inflammation, tissue remodeling, and disease progression.

Apoptosis is a controlled, energy-dependent process characterized by cell shrinkage, chromatin condensation, DNA fragmentation, and membrane blebbing with intact organelles until phagocytosis. It proceeds via intrinsic (mitochondrial) and extrinsic (death receptor) pathways, both converging on caspase proteases. The intrinsic pathway responds to cellular stress with mitochondrial outer membrane permeabilization and cytochrome c release; the extrinsic pathway engages death receptors such as Fas, activating initiator caspases.

Necrosis denotes rapid, uncontrolled cell breakdown often due to severe injury, releasing intracellular contents and provoking inflammation. Regulated necrosis pathways, including necroptosis (RIPK1/RIPK3/MLKL) and pyroptosis (inflammasome activation and gasdermins), blend features of necrosis with programmed signaling and inflammatory outcomes. Ferroptosis is driven by iron-dependent lipid peroxidation and distinct metabolic triggers. These forms influence immunity and tissue damage in disease.

Autophagy is a lysosome-dependent process for recycling cytoplasmic material, generally promoting survival during nutrient stress. Under certain conditions it can contribute to cell death, a concept known as autophagic cell death, though this remains debated and often reflects concurrent pathways rather than a separate mechanism.

Studying cell death informs cancer therapy, neurodegeneration, ischemia, and inflammatory diseases. Common research methods include assays for caspase activity, TUNEL DNA fragmentation, Annexin V binding, and monitoring autophagic flux through LC3 and p62. Understanding how cells die helps clarify developmental biology and disease mechanisms, as well as strategies to modulate death pathways therapeutically.