Every day, billions of cells die in your body, but not all meet their end in the same way. Some cells fade away quietly, while others go out dramatically in response to injury or infection. In recent years, scientists have discovered a vast range of cell death types, with over 20 different classifications now identified. Understanding these diverse death mechanisms could help researchers develop treatments for infections, autoimmune diseases, and cancers by preserving healthy cells and targeting harmful ones.
Accidental Cell Death: Necrosis
Cells can die accidentally through a process called necrosis. Necrosis happens when cells are exposed to severe trauma, such as being deprived of oxygen, infected by microbes, or physically injured. This form of cell death isn’t pretty—damaged cells swell and burst, releasing their contents and sparking inflammation in surrounding tissues. One example is gangrene, where oxygen-deprived cells begin to rot. Other necrosis types include the “caseous” necrosis of tuberculosis-infected lung cells, where they become soft and white, resembling cheese.
Programmed Cell Death: Apoptosis
Unlike necrosis, apoptosis is an orderly form of cell death. Cells initiate this process when they have outlived their usefulness or suffer irreparable damage. Apoptosis is a silent and tidy form of cell death that doesn’t provoke an immune response. In apoptosis, the cell shrinks, breaks up into pieces, and is consumed by neighboring cells, leaving tissues undisturbed. This process is crucial for normal development, as in the transformation of tadpoles into frogs or the shaping of fingers by removing webbing in human embryos.
Alert Mechanisms: Necroptosis and Pyroptosis
Cells sometimes die in ways designed to alert the immune system, such as necroptosis and pyroptosis. These forms of cell death occur when cells are infected or in danger, effectively sacrificing themselves to protect neighboring cells. In necroptosis, a cell swells and its outer membrane ruptures, spilling its contents in a mix of necrosis and apoptosis features. Pyroptosis is even more dramatic, causing a cell to swell, burst, and release molecules that signal the immune system to respond. Both forms of death can help combat infections, but excessive necroptosis or pyroptosis can lead to prolonged inflammation and autoimmune disorders.
A Mix of Mechanisms: PANoptosis
Some immune cells combine features of multiple death types in a process known as PANoptosis, which mixes apoptosis, necroptosis, and pyroptosis. Cells undergoing PANoptosis form a structure called the PANoptosome, which enables them to initiate multiple death pathways simultaneously. This form of cell death is a valuable defense against pathogens, as it provides cells with multiple ways to die, even if certain mechanisms are disabled by an infection.
Extreme Sacrifice: NETosis
White blood cells known as neutrophils employ a unique death mechanism called NETosis. When neutrophils encounter pathogens too large or numerous to consume, they release a net of DNA, ensnaring the invaders and preventing their spread. This act of self-sacrifice leaves the neutrophil dead or dying but helps eliminate pathogens more effectively.
Metal-Induced Deaths: Cuproptosis and Ferroptosis
In recent years, scientists have discovered two new metal-induced cell death types—cuproptosis and ferroptosis. Cuproptosis occurs when cells are overwhelmed with copper, causing cancer cells to die. Ferroptosis is triggered by iron and targets not only cancer cells but also cells in organs like the brain and liver. Research is ongoing to find ways to use these death mechanisms in cancer treatment by designing drugs that trigger ferroptosis or cuproptosis in cancer cells.
Cannibalistic Death: Entosis
Some cells engage in a behavior called entosis, where they are engulfed by other cells. The engulfed cell may starve and die or be digested by its host cell, although in some cases, it can survive and eventually break free. Entosis may provide cancer cells with a temporary hiding spot from the immune system or drug therapies.
The Many Faces of Cell Death
Each mode of cell death serves a purpose, helping cells protect the body or remove themselves when they become a liability. The evolution of multiple cell death mechanisms reflects an arms race between cells and pathogens, with cells developing numerous ways to die if attacked or hijacked. This diversity in cell death modes reveals how integral death is to the survival and adaptation of organisms, offering researchers new pathways for medical advancements.
Exploring cell death helps scientists understand life better. As author Haruki Murakami aptly noted, “Death exists, not as the opposite but as a part of life.”
