Lysosome

They are dense, spherical vacuoles bounded by a single membrane. The area within the membrane (the lumen) houses all the hydrolytic enzymes. The membranous sac helps to keep the enzymes separate from the rest of the cell, protecting the cell from destruction. The lysosome size typically ranges between 0.1 – 0.6 μm, with the largest being 1.2 μm.

The lysosome membrane comprises a lipid bilayer similar to a cell membrane containing hydrophilic phosphate group heads, a glycerol molecule, and hydrophobic fatty acid tails. The pH of the lumen lies between 4.5 and 5.0 and thus is acidic. It is similar to the pH of the acids found in the stomach.

As we know, lysosomes mainly work to remove unwanted substances from within the cell by processing unwanted materials and degrading them. However, sometimes the digestive enzymes end up damaging the lysosomes. It can be fatal and can cause the cell to die. The process is performed through autolysis (‘auto’ means ‘self’, and ‘lysis’ means ‘the disintegration of the cell by destroying its cell membrane’).

Lysosomes bud off the Golgi apparatus as sacs or vesicles. The hydrolytic enzymes within them form in the endoplasmic reticulum.

Lysosomes are formed by the union of transport vesicles that bud off from the trans-Golgi apparatus as sacs or vesicles with endosomes, which contain molecules taken up by endocytosis at the plasma membrane. The hydrolytic enzymes within the lysosome are formed in the endoplasmic reticulum.

Lysosomes are responsible for three main functions:

1. Digestion of Macromolecules

One of the significant purposes of the lysosome is the digestion of foreign molecules taken up inside the cell by endocytosis. Lysosomes contain about 50 hydrolyzing enzymes that digest macromolecules (nucleic acid, proteins, carbohydrates, and lipids) by hydrolysis.

Nucleic acids are broken down into nucleotides by nucleases, proteins into amino acids by peptidases, carbohydrates into simple sugars by amylases, and lipids into fatty acids and glycerol by lipases. These processes release energy that the cell requires for performing various cellular activities.

These recycled monomers are also used to synthesize macromolecules when needed by the cell or are released outside the cell as waste products.

2. Intracellular Transport by Endocytosis

As a part of the endomembrane system, the lysosome, Golgi apparatus, and endoplasmic reticulum exchange and digest materials within and outside the cell. The lysosome also maintains the cell’s internal milieu. The steps are:

1. Materials outside the cell are taken up in clathrin-coated endocytic vesicles that bud from the plasma membrane and fuse with early endosomes.
2. The cell membrane recycles membrane components, and the early endosomes gradually mature into late endosomes, which act as lysosome precursors. During endosomal maturation, the internal pH reaches almost 5.5, which helps deliver lysosomal acid hydrolases from the trans-Golgi network.
3. Acid hydrolases move towards lysosomes by mannose-6-phosphate residues recognized by mannose-6-phosphate receptors in the trans-Golgi network and packaged into clathrin-coated vesicles.
4. After removing the clathrin coat, the vesicle fuses with the late endosomes. The acidic pH causes the hydrolases to dissociate from the mannose-6-phosphate receptor and release into the lumen of the endosome.
5. Late endosomes then mature into lysosomes acquiring the acid hydrolases, which digest the foreign molecules initially taken up by endocytosis.

3. Phagocytosis and Autophagy

Apart from degrading the foreign molecules by endocytosis, digesting materials through phagocytosis and autophagy helps to protect the cell from large particle invasions such as pathogens and remove aged cells and cell debris.

In phagocytosis, specialized antigen-presenting cells like macrophages take up and degrade large molecules that need immediate removal from the body. Such molecules are taken up in phagocytic vacuoles known as phagosomes which then fuse with lysosomes, resulting in the digestion of the particle. The lysosome helping in such digestion is called phagolysosome.

Lysosomes are also involved in autophagy, a process by which cells destroy old, abnormal, or damaged proteins and other substances in their cytoplasm that helps recycle cellular components in an organism.

Besides the above functions, lysosomes are also involved in various cellular processes such as secretion, plasma membrane repair, apoptosis, cell signaling, and energy metabolism.

4. Platform for Intracellular Signal Transduction

Lysosomes can sense nutrients and thus regulate cell proliferation and growth with the help of signaling cascades like PI3K/AKT by activating receptor tyrosine kinases (RTKs) and epidermal growth factor receptors (EGFRs), among others.

Mutations in the genes encoding the hydrolytic enzymes cause more than 30 human genetic diseases, called lysosomal storage diseases (LSD). Such disorders are caused due to accumulation of undegraded material within the lysosome.

Most of these diseases occur due to deficiencies in single lysosomal enzymes. For example, Gaucher’s disease, the most common LSD, results from a gene mutation that encodes for an enzyme required to break down glycolipids.