Lysosomes are organelles in the cells of living organisms with formed nuclei (eukaryotes). Lysosomes are vesicles of a cell that are enclosed by a membrane and contain digestive enzymes. The function of lysosomes, which are maintained in an acidic environment, is to break down endogenous and exogenous substances and to initiate cellular destruction (apoptosis) when necessary.
What is a lysosome?
Lysosomes are vesicles, small cellular inclusions in eukaryotic cells that are surrounded by a membrane and contain a wide variety of intracellular hydrolytic digestive enzymes inside them. These are proteases, nucleases, and lipases, which are digestive enzymes that can break down and degrade proteins, nucleic acids, and lipids. The fragments are either broken down further and partially disposed of or reused by the metabolism, recycled so to speak. Lysosomes are therefore also referred to as the cell’s own stomach. The interior of the lysosomes, with a diameter of 0.1 to 1.1 micrometers, is maintained in an acidic environment with a pH of 4.5 to 5.0 by the activity of proton pumps. The highly acidic environment serves the cell’s self-protection, because enzymes are active only in an acidic environment. If a lysosome empties its enzymes into the pH-neutral cytosol, they are immediately deactivated and are harmless to the cell. To prevent the membrane itself from being attacked by the digestive enzymes, the membrane proteins are heavily glycosylated toward the inside.
Function, action, and tasks
The main function of lysosomes is to provide hydrolytic digestive enzymes to degrade proteins, nucleic acids, and lipids on demand. These can be substances foreign to the cell or substances that are intrinsic to the cell. The degradation of cell-own substances also includes apoptosis, the pre-programmed cell death in which the lysosomes with their enzymes assume an essential technical function. Particles foreign to the cell, which are located in the extracellular space and are intended for degradation, are first transported into the cell by endocytosis. The outer cell membrane bulges outward, flows around the substance to be degraded, and then splits off from the cell membrane as an independent vesicle. The vesicles fuse with lysosomes so that the degradation process can begin. The process of endocytosis and fusion with a lysosome always occurs without direct contact with the cytoplasm and is comparable to phagocytosis. In the course of independent cell renewal, other organelles and components of the cytosol are also supplied to the lysosomes for “fragmentation”. Usually, the fragments are reused, i.e. recycled, for the rebuilding of amino acids, proteins, nucleic acids and carbohydrates. Lysosomes also play an important role in apoptosis, or programmed cell death. The cell that has received the signal for apoptosis is shrunk and disassembled following a specific program, without any parts of the cell entering the extracellular space, where inflammatory reactions would immediately take place.
Formation, occurrence, properties, and optimal values
Lysosomes conveniently occur in every cell of eukaryotes with very few exceptions. Only the number of lysosomes per cell varies with cell type and with the cell’s tasks in the tissue. The hydrolytic enzymes and the proteins of the lysosomal membrane are synthesized by ribosomes at the endoplasmic reticulum (ER). They are then labeled in the trans-Golgi apparatus so that they are not haphazardly shipped to any lysosomes. The most important role in labeling is played by a phosphotransferase and another enzyme that completes the labeling process. The acidic environment within the lysosomes is ensured by a V-type ATPase. The enzyme cleaves 2 H+ ions from ATP via the process of hydrolysis and transports them to the lysosome. Lysosomes are involved in very many internal and external metabolic processes. A direct or indirect measurement of their number is not possible and would have little significance. Therefore, no statement can be made about an optimal number of lysosomes. Any dysfunctions of the lysosomes usually make themselves seriously felt.
Diseases and disorders
There are several known functional disorders of lysosomes that lead to serious diseases. A very rarely occurring – genetic – dysfunction is caused by a defect in phosphotransferase.The non-functional enzyme leads to an uncontrolled release of the lysosomal enzymes into the extracellular matrix. At the same time, there is an accumulation of lipids, mucopolysaccharides and glycoproteins in the lysosomes, which are actually intended for breakdown and degradation. However, since there are no digestive enzymes due to their misdirection, the substances accumulate more and more in the lysosomes. This autosomal, recessively inherited lysosomal storage disease, called I-cell disease, is due to a mutation of the GNPTAB gene. Other lysosomal storage diseases are known, but these are based on incorrectly synthesized hydrolases. Similar to I-cell disease, there is accumulation of undegraded proteins, nucleic acids, and lipids. All lysosomal storage diseases have in common that the ratio of substances introduced and excreted from the lysosomes is disturbed to the detriment of the substances to be excreted. A real congestion occurs within the lysosomes. The storage diseases usually take a serious course and are not curable in the sense of eliminating the cause. There is a further risk when taking weakly alkaline, lipophilic drugs. Although they can pass through the membranes of the lysosomes from the outside to the inside in neutral form, they cannot pass in the opposite direction if they are protonated by the acidic environment inside the lysosomes, so that lysosomotropy, an accumulation of the drugs in the lysosomes, can occur. The drugs can reach a concentration in lysosomes 100 to 1000 times the concentration in blood plasma.
