Part of the TeachMe Series

Lysosomes

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Original Author(s): Arjun Nehra
Last updated: 23rd May 2020
Revisions: 13

Original Author(s): Arjun Nehra
Last updated: 23rd May 2020
Revisions: 13

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Lysosomes are spherical, membrane bound organelles that are generated by the golgi apparatus. They contain hydrolytic enzymes, and so function as part of the recycling system of the cell.

In this article, we will look at the structure, synthesis and function of lysosomes, and we will consider their relevance to clinical practice.

Structure

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.

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 initiatiation 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.

Figure 1 – Diagram of the endomembrane system

Function

The hydrolytic enzymes contained within the lysosome allow foreign particles to be destroyed. Lysosomes play an important role in phagocytosis. When macrophages phagocytose foreign particles, they contain them within a phagosome. The phagosome will then bind with a lysosome to form a phagolysosome.

These enzymes are critical in oxygen-independent killing mechanisms. Lysosomes also help to defend against pathogen entry via endocytosis by degrading pathogens before they reach the cytoplasm.

Figure 2 – The role of the lysosome in phagocytosis

Clinical Relevance

I-cell disease

This is caused by genetic defects in the N-acetylglucosamine phosphotransferase enzyme. This enzyme is vital for the addition of mannose-6-phosphate to lysosome-targeted proteins. This results in lysosomal enzymes not being properly targeted. As a result significant amounts are found in both the urine and the blood stream.

Lysosomal Storage Disease

These are a group of genetic conditions affecting lysosomes. The condition vary widely in signs, symptoms and patient demographics. There are several classifications; the most common of these conditions is Gaucher’s disease. It is caused by a deficiency of the beta-glucocerebrosidase. This enzyme is required to break down glucocerebroside. Without this enzyme, the glucocerebroside is able to accumulate within cells, which can damaging them. Symptoms include hepatosplenomegaly and anaemia.

Fig 3 – Micrograph of necrotic bone tissue in Gaucher Disease