Infographic: How Cells Cheat Death
Infographic: How Cells Cheat Death

Infographic: How Cells Cheat Death

Apoptosis and other types of programmed cell death appear to be reversible.

Feb 1, 2019
Charles Q. Choi

Apoptosis is triggered many different ways, but they all ultimately activate enzymes known as caspases that disrupt a cell’s DNA, organelles, and cytoskeleton. Caspases also recruit other cells to eat the dying cell’s remains. Even after commencing this suicidal process, cells can recover through a recently discovered process dubbed anastasis. But if anastasis happens late in apoptosis, the surviving cells may carry major chromosomal scars and other genetic defects that can lead to malignancy.

Apoptosis

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1Dozens of known triggers can initiate apoptosis. Once started, apoptosis regulators can spark mitochondrial outer membrane permeabilization (MOMP), a critical step in fragmenting mitochondria.
2MOMP releases cytochrome c and other factors that trigger the formation of a protein structure called the apoptosome that can activate caspases.
3Caspases cleave proteins involved in DNA repair while activating an enzyme that attacks DNA.
4Caspases also attack the cytoskeletal scaffolds of cells, causing them to shrink and deform.
5The membrane molecule phosphatidylserine flips from the inner to the outer surface of the cell to signal phagocytes to engulf the dying cell.

Anatasis

© lisa clark
1A number of heat-shock proteins can suppress MOMP and caspase activation.
2Fragmented mitochondria glue themselves back together, while a subset of mitochondria remain intact or partially functional to supply energy to help cells recover.
3Messenger RNAs that accumulate before the cells die from apoptosis could support a quick recovery.
4Damaged proteins, mitochondria, and other cellular components are removed, possibly via autophagy and other mechanisms.
5Cells lose the phosphatidylserine “eat me” signal from their surfaces.
6Anastasis can induce angiogenesis and cell migration, which could enhance nutrient absorption and remove waste resulting from apopto­sis. It can also arrest the cell cycle to give the cell time to repair.

Other Forms of Cell Death Reversal

In addition to apoptosis, scientists have proposed more than 20 other regulated forms of cell death. Increasingly, researchers find some of these other kinds of cell death are also reversible.

Entosis

In entosis, one cell engulfs another living cell, which is then killed and digested by lysosomes. Sometimes engulfed cells survive, even proliferating within their cellular captor or escaping altogether.

© lisa clark

Necroptosis

Necroptosis is a programmed version of necrosis, a form of cell death linked with uncontrolled reactions to injuries or stress. The process involves the protein MLKL poking holes in the plasma membrane, which causes the cells to rupture. However, the cell can blunt this process through the ESCRT-III protein complex, which isolates these holes onto bubbles in the plasma membrane. Shedding these bubbles then repairs the cells, a process scientists dubbed “resuscitation.”

© lisa clark

Ferroptosis

Ferroptosis is a regulated form of cell death that is dependent on iron. Cells initiate this pathway when normal uptake and metabolism of the amino acid cysteine (cystine is the oxidized dimer form of cysteine) is disturbed. Once triggered, ferroptosis will result in cell death in a few hours. However, researchers can administer lipophilic antioxidants or iron chelators to completely protect cells from succumbing to this form of cell death.

© lisa clark

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