Lysosome - Structure and Function
Introduction
Lysosomes are membrane-bound, dense granular structures containing hydrolytic enzymes responsible mainly for intracellular and extracellular digestion. The word “lysosome” is made up of two words “lysis” meaning breakdown and “soma” meaning body. It is an important cell organelle responsible for the inter and extracellular breakdown of substances.
They are more commonly found in animal cells while only in some lower plant groups ( slime molds and saprophytic fungi). Lysosomes occur freely in the cytoplasm. In animals, found in almost all cells except in the RBCs. They are found in most abundant numbers in cells related to enzymatic reactions such as liver cells, pancreatic cells, kidney cells, spleen cells, leucocytes, macrophages, etc.
Structure of Lysosomes
Lysosomes are acidic membrane-bound organelles found within cells, usually around 1 micrometre in length. Lysosomes contain numerous hydrolytic enzymes which catalyse hydrolysis reactions.
The membrane surrounding the lysosome is vital to ensure these enzymes do not leak out into the cytoplasm and damage the cell from within. In order to maintain the acidic pH of the lysosome, protons are actively transported into the organelle across the lysosomal membrane.
Lysosomes are without any characteristic shape or structure i.e. they are pleomorphic They are mostly globular or granular in appearance. It is 0.2-0.5 μm in size and is surrounded by a single lipoprotein membrane unique in composition.
Diagram of Lysosomes
The membrane contains highly glycosylated lysosomal associated membrane proteins (LAMP) and Lysosomal integral membrane proteins (LIMP).
LAMPs and LIMPs form a coat on the inner surface of the membrane. They protect the membrane from attack by the numerous hydrolytic enzymes retained inside. The lysosomal membrane has a hydrogen proton pump which is responsible for maintaining pH conditions of the enzyme The acidic medium maintained by the proton pump that pumps H+ inside the lumen, ensures the functionality of the lysosomal enzymes. Inside the membrane, the organelle contains enzymes in the crystalline form.
Lysosomal Enzymes
For degradation of extra and intracellular material, lysosomes filled with enzymes called hydrolases. It contains about 40 varieties of enzymes which are classified into the following main types, namely:
Proteases, which digest proteins
Lipases, which digests lipids
Amylase, which digests carbohydrates
Nucleases, which digest nucleic acids
Phosphoric acid monoesters
Collectively the group of enzymes is called hydrolases which cause cleavage of substrates by the addition of water molecules. Most of the lysosomal enzymes function in the acidic medium.
Types of Lysosomes
Primary Lysosomes
Small sac-like structures enclosing enzymes synthesized by the rough endoplasmic reticulum.
Simply called as storage granules storing enzymes.
Secondary Lysosomes
Formed by the fusion of primary lysosome with phagosomes.
Contain engulfed material plus enzymes.
Materials are progressively digested.
Synthesis
The lysosome and the enzymes within it are synthesised separately. Lysosomal proteins are formed in the same way as any other protein. The first step is the initiation of mRNA strand production from relevant DNA segments. The mRNA strands proceed to the rough endoplasmic reticulum, where ribosomes construct the hydrolytic enzymes.
Importantly, these are tagged with mannose-6-phosphate within the golgi apparatus to target them to the lysosome. As a result, vesicles containing these enzymes bud off from the golgi apparatus. Two enzymes are responsible for the attachment of the mannose-6-phosphate tag: N-acetylglucosamine phosphotransferase and N-acetylglucosamine phosphoglycosidase.
This vesicle, now in the cytoplasm, then binds with a late endosome which is another acidic, membrane-bound organelle. The late endosome has proton pumps within its membrane that keep its internal environment acidic. The low pH causes dissociation of the protein from the mannose-6-phosphate receptor. This receptor can then be recycled back to the golgi apparatus.
The phosphate group is also removed from the mannose-6-phosphate tag, to prevent the whole protein returning to the golgi apparatus. The late endosome can eventually mature into a lysosome, after it has received the enzymes from the golgi apparatus.
Functions of Lysosomes
Lysosomes serve two major functions:
Intracellular Digestion
To digest food, the lysosome membrane fuses with the membrane of food vacuole and squirts the enzymes inside.
The digested food then diffuses through the vacuole membrane and enters the cell to be used for energy and growth.
Autolytic Action
Cell organelles that need to be ridden are covered by vesicles or vacuoles by the process of autophagy to form autophagosome.
The autophagosome is then destroyed by the action of lysosomal enzymes.
Processes in which lysosomes play crucial roles include:
a. Heterophagy
The taking into the cell of exogenous material by phagocytosis or pinocytosis and the digestion of the ingested material after fusion of the newly formed vacuole with a lysosome.
b. Autophagy
A normal physiological process that deals with the destruction of cells in the body. It is essential for maintaining homeostasis, for normal functioning by protein degradation, turnover of destroyed cell organelles for new cell formation
c. Extracellular Digestion
Primary lysosomes secrete hydrolases outside by exocytosis resulting in degradation of extracellular materials.
Eg. Saprophytic fungi
d. Autolysis
It refers to the killing of an entire set of cells by the breakdown of the lysosomal membrane. It occurs during amphibian and insect metamorphosis.
e. Fertilization
The acrosome of the sperm head is a giant lysosome that ruptures and releases enzymes on the surface of the egg. This provides the way for sperm entry into the egg by digesting the egg membrane.
f. As Janitors of the Cell
Lysosomes remove ‘junk’ that may accumulate in the cell helping to prevent diseases.
Lysosomal Disease
Nuclear genes organize the production of enzymes in the lysosomes. Nuclear genes are those genes that are being located within the nucleus of a cell, especially in eukaryotes. If there are any mutations in these genes, it will result in the emergence of a lot of human genetic ailments which are collectively called LSD (lysosomal storage diseases).
Lysosomes as the Therapeutic Targets
There are a lot of lysosomal pathways and their components that can represent the potential pharmacological targets for a huge number of diseases. When we consider lysosomes as the targets, it is very important to note down the need for specificity, i.eThe agents will not target all lysosomes, but they will especially target those lysosomes which are defective in a few organs, cells, or tissues. For several reasons, it is very important to target lysosomes and not to target the whole autophagy process. Firstly, regarding safety, the important role of lysosomes in many key physiological processes means that the therapeutic windows for the intervention of pharmacology with unacceptable side effects may be limited.
Summary of Lysosomes
Lysosomes are cell organelles almost exclusively found in eukaryotic animal cells
Lysosomes are membrane-bound spherical sacs crammed with hydrolytic enzymes
These enzymes can break down many sorts of biomolecules like proteins and fats
Lysosomes are known as the ‘Suicidal Bags’ as they have the capacity to destroy the cell wall with its digestive enzymes, causing autolysis of the cell
Lysosomal enzymes are synthesized within the rough endoplasmic reticulum, where they've brought in by the Golgi body through tiny vesicles. It eventually merges with bigger acidic vesicles
Mutations of the nuclear gene may end in the emergence of rare, diverse human genetic ailments, which are called lysosomal storage diseases or LSD
