The lysosomes are tiny membrane-bound vesicles involved in intracellular digestion. They contain a variety of hydrolytic enzymes that remain active under acidic conditions. The lysosomal lumen is maintained at an acidic pH (around 5) by an ATP-driven proton pump in the membrane.
Thus, these remarkable organelles are primarily meant for the digestion of a variety of biological materials and secondarily cause aging and death of animal cells and also a variety of human diseases such as cancer, gout, Pompe’s disease, silicosis and I-cell disease.
History of Lysosomes
During early electron microscopic studies, rounded dense bodies were observed in rat liver cells. These bodies were initially described as “perinuclear dense bodies”. by C. de Duve, in 1955, renamed these organelles as ‘lysosomes’ to indicate that the internal digestive enzymes only became apparent when the membrane of these organelles was lysed.
However, the term lysosome means lytic body having digestive enzymes capable of lysis (viz., dissolution of a cell or tissue. Lysosomes were investigated according to following two schools:
- C. de Duve and his coworkers worked in Belgium and their approach was biochemical one.
- Alex Novikoff and his research group (1962, 1964) worked in the United States and their approach was morphological and cytochemical.
For the discovery of lysosomes and a brilliant series of experiments on them, de Duve shared the 1974 Nobel Prize for physiology with Palade and Claude, both were pioneer cell biologists.
Where lysosome found?
The lysosomes occur in most animals and few plant cells. They are absent in bacteria and mature mammalian erythrocytes. Few lysosomes occur in muscle cells or in the acinar cells of the pancreas.
Leucocytes, especially granulocytes are a particularly rich source of lysosomes. Their lysosomes are so large-sized that they can be observed under the light microscope. Lysosomes are also numerous in epithelial cells of absorptive, secretory, and excretory organs (e.g., intestine, liver, kidney, etc.).
They occur in abundance in the epithelial cells of lungs and uterus. Lastly, phagocytic cells and cells of reticuloendothelial system (e.g., bone marrow, spleen and liver) are also rich in lysosomes.
Structure of Lysosome
The lysosomes are round vacuolar structures which remain filled with dense material and are bounded by single unit membrane. Their shape and density vary greatly. Lysosomes are 0.2 to 0.5μm in size.
Since, size and shape of lysosomes vary from cell to cell and time to time (i.e. they are polymorphic), their identification becomes difficult. However, on the basis of the following three criteria, a cellular entity can be identified as a lysosome:
- It should be bound by a limiting membrane
- It should contain two or more acid hydrolases; and
- It should demonstrate the property of enzyme latency when treated in a way that adversely affects the organelle’s membrane structure.
Enzymes of Lysosome
According to a recent estimate, a lysosome may contain up to 40 types of hydrolytic enzymes. They include:
All lysosomal enzymes are acid hydrolases, optimally active at the pH5 maintained within lysosomes. The membrane of the lysosome normally keeps the enzymes latent and out of the cytoplasmic matrix or cytosol (whose pH is about ~7.2), but the acid dependency of lysosomal enzymes protects the contents of the cytosol (cytoplasmic matrix) against any damage even if leakage of lysosomal enzymes should occur.
The so-called latency of the lysosomal enzymes is due to the presence of the membrane which is resistant to the enzymes that it encloses. Most probably this is due to the fact that most lysosomal hydrolases are membrane-bound, which may prevent the active centers of enzymes to gain access to susceptible groups in the membrane.
Membrane of Lysosomes
The lysosomal membrane is slightly thicker than that of mitochondria. It contains substantial amounts of carbohydrate material, particularly sialic acid. In fact, most lysosomal membrane proteins are unusually highly glycosylated, which may help protect them from the lysosomal proteases in the lumen.
The lysosomal membrane has another unique property of fusing with other membranes of the cell. This property of fusion has been attributed to the high proportion of membrane lipids present in the micellar configuration.
Surface active agents such as liposoluble vitamins (A, K, D and E) and steroid sex hormones have a destabilizing influence, causing release of lysosomal enzymes due to rupture of lysosomal membranes.
On the contrary, the cortisone, hydrocortisone and other drugs tend to stabilize the lysosomal membrane and have an anti-inflammatory effect on the tissue. The entire process of digestion is carried out within the lysosome. Most lysosomal enzymes act in an acid medium. Acidification of lysosomal contents depends on an
ATP-dependent proton pump which is present in the membrane of the lysosome and accumulates H+ inside the organelle. Lysosomal membrane also contains transport proteins that allow the final products of digestion of macromolecules to escape so that they can be either excreted or reutilized by the cell.
Types of lysosomes
Lysosomes are extremely dynamic organelles, exhibiting polymorphism in their morphology. Following four types of lysosomes have been recognized in different types of cells or at different times in the same cell.
Of these, only the first is the primary lysosome, the other three have been grouped together as secondary lysosomes.
1. Primary Lysosomes
These are also called storage granules, protolysosomes or virgin lysosomes. Primary lysosomes are newly formed organelles bounded by a single membrane and typically having a diameter of 100 nm.
They contain the degradative enzymes which have not participated in any digestive process. Each primary lysosome contains one type of enzyme or another and it is only in the secondary lysosome that the full complement of acid hydrolases is present.
They are also called heterophagic vacuoles, heterolysosomes or phagolysosomes. Heterophagosomes are formed by the fusion of primary lysosomes with cytoplasmic vacuoles containing extracellular substances brought into the cell by any of a variety of endocytic processes.
The digestion of engulfed substances takes place by the enzymatic activities of the hydrolytic enzymes of the secondary lysosomes. The digested material has low molecular weight and readily passess through the membrane of the lysosomes to become the part of the matrix.
They are also called autophagic vacuole, cytolysosomes or autolysosomes. Primary lysosomes are able to digest intracellular structures including mitochondria, ribosomes, peroxisomes, and glycogen granules.
Such autodigestion (called autophagy) of cellular organelles is a normal event during cell growth and repair and is especially prevalent in differentiating and dedifferentiating tissues (e.g., cells undergoing programmed death during metamorphosis or regeneration) and tissue under stress.
Autophagy takes several forms. In some cases, the lysosome appears to flow around the cell structure and fuse, enclosing it in a double membrane sac, the lysosomal enzymes being initially confined between the membranes.
The inner membrane then breaks down and the enzymes are able to penetrate to the enclosed organelle.In other cases, the organelle to be digested is first encased by smooth ER, forming a vesicle that fuses with a primary lysosome.
Lysosomes also regularly engulf bits of cytosol (cytoplasmic matrix) which is degraded by a process, called microautophagy. As digestion proceeds, it becomes increasingly difficult to identify the nature of the original secondary lysosome (i.e., heterophagosome or autophagosome), and the more general term digestive vacuole is used to describe the organelle at this stage.
4. Residual Bodies
They are also called telolysosomes or dense bodies. Residual bodies are formed if the digestion inside the food vacuole is incomplete. Incomplete digestion may be due to absence of some lysosomal enzymes.
The undigested food is present in the digestive vacuole as the residues and may take the form of whorls of membranes, grains, amorphous masses, ferritin-like or myelin figures. Residual bodies are large, irregular in shape and are usually quite electron-dense.
In some cells, such as Amoeba and other potozoa, these residual bodies are eliminated by defecation. In other cells, residual bodies may remain for a long time and may load the cells to result in their aging.
For example, pigment inclusions (age pigment or lipofuscin granules) found in nerve cells (also in liver cells, heart cells and muscle cells) of old animals may be due to the accumulation of residual bodies.
Origin of Lysosomes
The biogenesis (origin) of the lysosomes requires the synthesis of specialized lysosomal hydrolases and membrane proteins. Both classes of proteins are synthesized in the ER and transported through the Golgi apparatus, then transported from the trans-Golgi network to an intermediate compartment (an endolysosome) by means of transport vesicles.
The lysosomal enzymes are glycoproteins, containing N-linked oligosaccharides that are processed in a unique way in the cis Golgi so that their mannose residues are phosphorylated. This mannose 6-phosphate (M6P) groups are recognized by M6P-receptors (which are transmembrane proteins) in the trans-Golgi network that segregates the hydrolases and helps to package them into budding clathrin-coated vesicles which quickly lose their coats.
These transport vesicles containing the M6P-receptors act as shuttles that move the receptors back and forth between the trans Golgi network and endolysosomes. The low pH in the endolysosome dissociates the lysosomal hydrolases from this receptor, making the transport of the hydrolases unidirectional.
Function of Lysosomes
The important functions of lysosomes are as follows:
1. Digestion of large extracellular particles.
The lysosomes digest the food contents of the phagosomes or pinosomes. The lysosomes of leucocytes enable the latter to devour foreign proteins, bacteria, and viruses.
2. Digestion of intracellular substances.
In certain pathological conditions the lysosomes start to digest the various organelles of the cells and this process is known as autolysis or cellular autophagy. When a cell dies, the lysosome membrane ruptures and enzymes are liberated. These enzymes digest the dead cells. In the process of metamorphosis of amphibians and \tunicates many embryonic tissues, e.g., gills, fins, tail, etc., are digested by the lysosomes and utilized by the other cells.
4. Extracellular digestion.
The lysosomes of certain cells such as sperms discharge their enzymes outside the cell during the process of fertilization. The lysosomal enzymes digest the limiting membranes of the ovum and form penetration path in ovum for the sperms.
Acid hydrolases are released from osteoclasts and break down bone for the reabsorption; these cells also secrete lactic acid which makes the local pH enough for optimal enzyme activity. Likewise, preceding ossification (bone formation), fibroblasts release cathepsin D enzyme to break down the connective tissue