Lysosome

A lysosome (/ˈlaɪsəˌsoʊm/) is a membrane-bound organelle found in many animal cells. They are spherical vesicles that contain hydrolytic enzymes that can break down many kinds of biomolecules. A lysosome has a specific composition, of both its membrane proteins, and its lumenal proteins. The lumen's pH (~4.5–5.0) is optimal for the enzymes involved in hydrolysis, analogous to the activity of the stomach. Besides degradation of polymers, the lysosome is involved in various cell processes, including secretion, plasma membrane repair, cell signaling, and energy metabolism. Lysosomes act as the waste disposal system of the cell by digesting obsolete or un-used materials in the cytoplasm, from both inside and outside the cell. Material from outside the cell is taken-up through endocytosis, while material from the inside of the cell is digested through autophagy. The sizes of the organelles vary greatly—the larger ones can be more than 10 times the size of the smaller ones. They were discovered and named by Belgian biologist Christian de Duve, who eventually received the Nobel Prize in Physiology or Medicine in 1974. Lysosomes are known to contain more than 60 different enzymes, and have more than 50 membrane proteins. Enzymes of the lysosomes are synthesised in the rough endoplasmic reticulum. The enzymes are imported from the Golgi apparatus in small vesicles, which fuse with larger acidic vesicles. Enzymes destined for a lysosome are specifically tagged with the molecule mannose 6-phosphate, so that they are properly sorted into acidified vesicles. Synthesis of lysosomal enzymes is controlled by nuclear genes. Mutations in the genes for these enzymes are responsible for more than 30 different human genetic disorders, which are collectively known as lysosomal storage diseases. These diseases result from an accumulation of specific substrates, due to the inability to break them down. These genetic defects are related to several neurodegenerative disorders, cancers, cardiovascular diseases, and ageing-related diseases. Lysosomes should not be confused with liposomes, or with micelles. Christian de Duve, the chairman of the Laboratory of Physiological Chemistry at the Catholic University of Louvain in Belgium, had been studying the mechanism of action of a pancreatic hormone insulin in liver cells. By 1949, he and his team had focused on the enzyme called glucose 6-phosphatase, which is the first crucial enzyme in sugar metabolism and the target of insulin. They already suspected that this enzyme played a key role in regulating blood sugar levels. However, even after a series of experiments, they failed to purify and isolate the enzyme from the cellular extracts. Therefore, they tried a more arduous procedure of cell fractionation, by which cellular components are separated based on their sizes using centrifugation. They succeeded in detecting the enzyme activity from the microsomal fraction. This was the crucial step in the serendipitous discovery of lysosomes. To estimate this enzyme activity, they used that of standardised enzyme acid phosphatase, and found that the activity was only 10% of the expected value. One day, the enzyme activity of purified cell fractions which had been refrigerated for five days was measured. Surprisingly, the enzyme activity was increased to normal of that of the fresh sample. The result was the same no matter how many times they repeated the estimation, and led to the conclusion that a membrane-like barrier limited the accessibility of the enzyme to its substrate, and that the enzymes were able to diffuse after a few days (and react with their substrate). They described this membrane-like barrier as a 'saclike structure surrounded by a membrane and containing acid phosphatase.' It became clear that this enzyme from the cell fraction came from membranous fractions, which were definitely cell organelles, and in 1955 De Duve named them 'lysosomes' to reflect their digestive properties. The same year, Alex B. Novikoff from the University of Vermont visited de Duve's laboratory, and successfully obtained the first electron micrographs of the new organelle. Using a staining method for acid phosphatase, de Duve and Novikoff confirmed the location of the hydrolytic enzymes of lysosomes using light and electron microscopic studies. de Duve won the Nobel Prize in Physiology or Medicine in 1974 for this discovery.