Lysosome

Lysosome

The history of most cell organelles has been the early description by microscopists followed many years later by the isolation and the biochemical characterization. The lysosome is an exception in that it originated as a biochemical concept and the morphological identification followed. Among investigators isolating mitochondria and microsomes by differential centrifugation of cell homogenates, there was the disagreement as to which fraction contained the enzyme acid phosphatase. Some found it in the mitochondrial fraction, while others, using somewhat lower centrifugal force, found it in their microsome fraction. This problem was resolved by DeDuve and his associates, who were able to separate the classical mitochondrial fraction into the two subfractions. The lighter (L) fraction consisted of particles rich in acid phosphatase but it lacks the mitochondrial enzyme cytochrome oxidase. These particles, which also contained cathepsin, ribonuclease, the deoxyribonuclease, and the z /3-glucuronidase, were recognized as a new particulate component of cells distinct from the mitochondrial and were given the name lysosomes to draw the attention to their richness in hydrolytic enzymes. Another defining characteristic of the lysosomes was the fact that they were impermeable to the that of substrates and were enzymatically active in vitro only after the disruption or the treatment with a surface active agent. It was thus inferred that they must be enclosed by a membrane-like barrier. When the centrifugal pellets of fractions enriched in lysosomes were examined in thin sections with the electron microscope, the high proportion of the granules were obviously different from mitochondria. They had the dense heterogeneous content and that is postulated as they were enclosed by a membrane. Fortunately, a dependable cytochemical method was provided for the lysosomal enzyme acid phosphatase. Cytochemical observations at the light and the electron microscope level confirmed that the acid phosphatase of the liver was not localized in the mitochondria but in membrane-bounded dense bodies in the vicinity of the bile canaliculi. Unlike the mitochondria and other cell organelles which have the consistent, clearly defined and the easily recognizable structure, the granules exhibiting the acid phosphatase activity varied in size and were highly heterogeneous in the internal structure. Some were spherical with a uniform content of moderate density; others were irregular in the outline and contained aggregations of very dense granules in a less dense matrix. Others contained myelin figures or the crystalline inclusions. It was this extraordinary pleomorphism that had prevented cytologists from recognizing lysosomes as the distinct entity. This was the first instance of an organelle that could not be identified with confidence solely by the morphological criteria. Biochemical or cytochemical demonstration of acid hydrolase activity was required. By 1962, the number of hydrolytic enzymes identified had increased to 10. It was apparent that while most of these were present in all lysosomes, their proportions probably varied the considerably from tissue to tissue. The assembly of multiple acid hydrolases in the same organelle led naturally to the speculation that lysosomes functioned as an intracellular digestive system and that the substances degraded were either exogenous - brought into the cell by phagocytosis - or endogenous, involving the controlled autolytic elimination of other organelles and inclusions in the course of normal renewal or in response to an altered state of physiological activity. An essential feature of this concept was the belief that in their lysosomes cells contained the seeds of their own destruction. In normal function, it was assumed that the digestive processes had to be sequestered within membranes to protect the surrounding cytoplasm, but in pathological conditions autolysis of cells was a consequence of the breakdown of this protective barrier and release of digestive enzymes into the cytoplasm.

While the main site of the lysosomal function is intracellular, evidence has accumulated in recent years indicating that under certain conditions phagocytic cells can secrete their lysosomal enzymes. The secretion of collagenase and other proteases by osteoclasts is involved in the resorption of the matrix in the normal remodeling of bone. The binding of complement or antigen-antibody complexes to leukocytes or macrophages stimulates their secretion of hydrolases that may destroy basal laminae, cartilage matrix, collagen or elastin and result in damage to kidneys, joints, or lungs. The lysosomes that have been most thoroughly studied are those of hepatic cells which were first centrifugally isolated from the mitochondria1 fraction of liver homogenates. The primary lysosomes tend to have a dense homogeneous content but the secondary lysosomes may contain a variety of products of hydrolysis of differing density and texture. The majority of the membrane-bounded dense bodies in the accompanying figures are secondary 1ysosomes. In the absence of a universally applicable set of morphological criteria, identification of lysosomes rests upon a general resemblance to the dense particles comprising the "lysosome fraction" of liver homogenates. Since one of their defining characteristics is the presence of hydrolytic enzymes, verification of the lysosomal nature of cytoplasmic particles requires the cytochemical demonstration of their acid phosphatase or beta-glucuronidase activity. In the internal remodeling of cells associated with the diminished physiological activity, excess organelles are eliminated by autophagy. The organelle or inclusion to be destroyed is first surrounded by a membrane to form an autophagic vacuole. Lysosomes then fuse with it, discharging their hydrolytic enzymes into its interior. The origin of the membrane surrounding the material to be digested has not been established, but the fact that there are often two parallel limiting membranes suggests the possibility that a cistern of the smooth endoplasmic reticulum or GERL is involved. The accompanying micrographs present typical examples of autophagic vacuoles. The upper figures are of liver from an animal in the period of recovery after experimental induction of drug-metabolizing enzymes. The content of the autophagic vacuoles is mainly smooth endoplasmic reticulum and free ribosomes. In the figure at the lower left, a mitochondrion, and a peroxisome have been sequestered, and the autophagic vacuole at the lower right contains a mitochondrion in a more advanced state of dissolution but with cristae still identifiable.

References

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Kotpal, R L. Modern textbook of Zoology. Meerut, India: Rastogi Publication, n.d.

Rastogi, S C. Cell, and Molecular biology. New Delhi: New Age International (P) Limited, 2001.

Verma, P S, and V K Agrawal. cell biology,Genetics,Molecular Biology,Evolution, and Ecology. New Dehli, India: S. Chand and company Ltd., 2012.