Ultrastructural changes of the surface and cytoplasm
A cell entering apoptosis undergoes a series of morphological changes. First of all, specialized surface structures are lost: microvilli disappear, intercellular bridges and desmosomal contacts break down. The cell loses connection with its neighbors and acquires a rounded shape.
Inside, cytoplasmic condensation and a decrease in total volume occur. This process is ensured by two mechanisms:
- Dehydration due to the work of selective ion pumps regulating potassium and sodium exchange.
- Cross-linking of protein molecules using transglutaminase enzymes.
Unlike necrosis, activation of hydrolytic enzymes does not occur, so intracellular structures remain intact for a long time.
Transformation of organelles and the nucleus
Despite the overall cell shrinkage, mitochondria and other organelles retain their integrity. The smooth endoplasmic reticulum undergoes dilatation—it expands to form fluid-filled vesicles that are subsequently expelled outward. Ribosomes aggregate to form specific semi-crystalloid structures, and cytoskeleton elements form bundles of microfilaments arranged strictly parallel to the plasma membrane.
The nucleus undergoes fundamental changes. Under the action of $Ca^{2+}/Mg^{2+}$-dependent endonucleases, DNA is cleaved, forming uniform-sized fragments. Chromatin condenses into clumps and hemispheres, and osmiophilic bodies appear. Nuclear pores concentrate exclusively in areas where chromatin margination is absent. As a result, the nucleus shrinks, its contours become jagged, and it fragments.
Formation and fate of apoptotic bodies
The final stage of morphological rearrangements is the splitting of the cell into several fragments—apoptotic bodies. These are small, rounded formations with a high nuclear-cytoplasmic ratio.
Each body contains a set of intact organelles, a nuclear fragment surrounded by a double-contour membrane, as well as water, sodium, and chloride ions. The dense membrane plays a critical role: it isolates the contents from the immune system and prevents altered proteins from escaping into the extracellular space. This is why inflammation does not develop during apoptosis. In vivo, apoptotic bodies exist for only a few minutes, after which they are immediately phagocytosed by neighboring cells.
Genetic regulation and verification methods
Apoptosis is triggered by genetic rearrangements. Normally, the activation of cellular oncogenes (c-fos, c-myc, c-bcl-2) leads to proliferation. However, upon their simultaneous expression with the anti-oncogene p53, the cell dies. This indicates a close coordination of reproduction and death processes in the genetic apparatus.
For reliable morphological verification of the process, methods detecting specific DNA and enzyme changes are used:
- TUNEL assay (in situ uridine nucleotide end-labeling method). Detects unpaired DNA regions at sites cleaved by endonucleases. It allows visualization of cells with shrunken and pyknotic nuclei, as well as the apoptotic bodies themselves.
- Immunohistochemical methods (IHC). Used to detect specific enzymes of apoptosis, particularly caspases.
Comparative characteristics with necrosis
Apoptosis and necrosis are two fundamentally different forms of cell death. While necrosis covers a vast territory (ranging from part of a cell to an entire organ) and is accompanied by chaotic DNA breakdown with the activation of hydrolytic enzymes, apoptosis is a targeted process. It affects only individual cells, is characterized by ordered chromatin destruction, and the complete absence of an inflammatory response around the dead structure.
Briefly: answers to topical questions
What stages are distinguished in the process of apoptosis?
- Initiation.
- Programming.
- Execution of the program — direct cell death due to the activation of destructive enzymes.
- Removal of the dead cell — phagocytosis of apoptotic bodies.
What are the main pathways triggering apoptosis?
- Extrinsic (receptor-mediated) pathway — mediated by the interaction of a ligand with death receptors on the cell surface, leading to the activation of the caspase cascade.
- Intrinsic (mitochondrial) pathway — associated with increased mitochondrial membrane permeability, release of cytochrome c into the cytosol, and formation of the apoptosome.
Into which groups are the caspases involved in apoptosis divided?
- Initiator caspases — caspase 9 and caspase 8, which participate in the initiation of apoptosis.
- Executioner (effector) caspases — caspase 3 (the primary one), caspase 6, and caspase 7, which carry out the direct destruction of cellular structures.
Which cells act as phagocytes for apoptotic bodies?
- Specialized macrophages — phagocytose apoptotic bodies within tissues.
- Neighboring (non-inflammatory) cells — participate in the immediate phagocytosis of dead cell fragments.
To remember the essence of apoptosis, imagine careful packing before departure: the cell "slims down" (dehydration), neatly packs its belongings (intact organelles) into separate suitcases (apoptotic bodies), and quietly leaves without drawing the attention of neighbors (no inflammation).
Class and exam questions
Why is apoptosis difficult to observe under conventional light microscopy?
The process occurs very rapidly, and the resulting apoptotic bodies are phagocytosed by neighboring cells in a matter of minutes, leaving no traces in the tissue.
How does DNA fragmentation in apoptosis differ from that in necrosis?
During apoptosis, DNA is cleaved by endonucleases strictly between nucleosomes to form uniform fragments, whereas necrosis involves random breakdown of genetic material.
Which genes trigger the apoptotic process?
Cell death occurs upon the simultaneous activation of cellular oncogenes (e.g., c-fos, c-myc, c-bcl-2), which normally regulate proliferation, and the antioncogene p53.
What else to study on this topic
- The role of caspases in immunohistochemical verification of apoptosis
- Mechanisms of $Ca^{2+}/Mg^{2+}$-dependent endonuclease activity
- Genetic coordination of cell proliferation and death (interaction of oncogenes and p53)
- Principle of the in situ labeling method (TUNEL assay)
- Biochemical mechanisms of cytoplasmic condensation (the role of transglutaminases and ion pumps)
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