Necrosis: when a cell dies from trauma
Necrosis is a passive form of cell death that does not require energy (ATP) expenditure. This process is always associated with extreme damage or a sharp change in conditions, such as hypoxia (as in myocardial infarction).
Pathogenesis of necrosis:
- The integrity of the membranes (both the plasmalemma and organelles) is compromised.
- Water rushes into the cell, leading to swelling of the cell and nucleus, as well as organelle edema.
- Autolysis occurs: lysosomal enzymes escape into the cytoplasm and randomly digest the contents.
- The nucleus condenses and completely dissolves under the action of nucleases (karyolysis).
- The plasmalemma ruptures, and the cellular contents spill outward.
The main consequence of necrosis is the release of breakdown products into the intercellular environment, which damages neighboring cells and provokes the development of an inflammatory response.
Apoptosis: programmed self-destruction
Apoptosis is an evolutionarily developed, genetically controlled process of cell death. It requires energy expenditure and serves to eliminate dangerous or unnecessary cells. The main difference from necrosis is that the cell breaks down into neat membrane-bound fragments (apoptotic bodies). The contents do not spill out, no inflammation occurs, and the fragments are rapidly engulfed (phagocytized) by neighboring cells.
Triggers for apoptosis:
- Internal signals (intrinsic pathway): aging of long-lived (neurons) or rapidly renewing (epithelium) cells, as well as the accumulation of critical DNA mutations during division.
- External signals (extrinsic pathway): destruction of temporary embryonic structures, elimination of autoreactive immune cells, follicular atresia, and cell death due to a lack of growth factors. The signal may arrive via receptor binding to a specific ligand or due to the loss of contact with a survival factor.
Morphology and biochemical tools of apoptosis
Morphologically, apoptosis begins with chromatin condensation (it gathers into distinct clumps at the periphery of the nucleus). Then the cell shrinks (rather than swelling, as in necrosis), and the nucleus disintegrates. The plasmalemma forms invaginations, and the cell divides into apoptotic bodies.
The process is carried out using specific biochemical mechanisms:
- Caspases: a family of enzymes (proteases) that cleave nuclear proteins. They do not fully lyse the proteins, but rather cut them into large peptides.
- Nucleases: enzymes that cleave DNA strictly between nucleosomes, fragmenting the genetic material.
- Membrane proteins: translocate specific phospholipids to the outer layer of the apoptotic body membrane. This serves as an "eat-me signal" for macrophages.
Regulation of apoptosis: the role of p53 and mitochondria
The central regulator of apoptosis is the p53 protein. Its activity increases in response to chromosomal damage or the absence of growth factors. It is capable of arresting the cell cycle, inducing oxidative stress, and affecting the cellular microenvironment.
The main pathway for p53 signal transduction is the mitochondrial pathway. Mitochondrial membranes contain channels whose activity is controlled by regulatory proteins. Inhibitors (such as Bcl-2) close the channels, while activators (Bax) open them.
Under the action of p53, the channels open and mitochondrial proteins are released into the hyaloplasm: cytochrome c and AIF factor. They trigger the caspase cascade, which leads to chromosome breakdown, DNA fragmentation, and formation of apoptotic bodies.
Briefly: answers to topical questions
What pathways induce apoptosis other than the mitochondrial one?
In addition to the mitochondrial (intrinsic) pathway, there are extrinsic and perforin-granzyme pathways of apoptosis induction.
- The extrinsic pathway (receptor-mediated pathway) is mediated by the interaction of a death ligand with surface receptors (e.g., Fas receptors) containing an intracellular death domain.
- The perforin-granzyme pathway is carried out by immune cells by introducing enzymes through pores in the target cell membrane, which directly activates effector caspases.
What is the specific role of the AIF factor released from mitochondria during apoptosis?
The AIF factor acts as a mitochondrial protease whose release is a triggering event for apoptosis.
- AIF factor (Apoptosis-inducing factor) is a mitochondrial protein.
During programmed cell death, it is released from mitochondria into the hyaloplasm (cytosol) along with cytochrome c. This process occurs both in intrinsic apoptosis and during contact cytolysis. The exact biochemical function of this factor, aside from participating in the initiation of apoptosis, is not detailed in sources.
Necrosis: the cell "bursts" from water (swells), and everything around gets messy (inflammation). Apoptosis: the cell "dries out" (shrinks) and breaks down into neat cubes (bodies) that are quietly cleaned up by the janitors (macrophages).
Class and exam questions
How does apoptosis differ from necrosis in its effect on tissue?
Apoptosis does not cause inflammation because cell fragments remain enclosed within membranes and are rapidly phagocytized. Necrosis destroys membranes, spilling contents into the tissue, damaging neighbors, and triggering an inflammatory response.
Does cell death require energy expenditure?
It depends on the type of cell death. Necrosis is a passive process that does not require ATP. Apoptosis is an active genetic program that requires energy to function.
What happens to the nucleus during apoptosis and necrosis?
During apoptosis, chromatin gathers into distinct clumps at the periphery, and then the nucleus fragments (breaks into membrane-bound pieces). In necrosis, the nucleus simply dissolves under the action of enzymes (karyolysis).
Why are caspases needed?
These are proteolytic enzymes that act as the executioner mechanism in apoptosis. They cleave nuclear proteins into large peptides, facilitating cell fragmentation.
What else to study on this topic
- Mechanisms of the receptor phase of apoptosis ("extrinsic pathway")
- The MAPK cascade and Ras protein in the regulation of cell death
- Detailed action of DNA-protein kinase and the ATM enzyme
- Antitumor effects of the p53 protein
- The impact of apoptosis on embryogenesis (examples of structural reduction)
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