Lysosomes are membrane-bound organelles responsible for intracellular digestion of substances derived from both inside and outside the cell. Within their membrane an acidic interior (pH ~ 5) is maintained by the action of proton pumps in the membrane. The lysosomes contain a class of enzymes, hydrolases, that catalyse hydrolysis of covalent bonds in proteins, lipids, carbohydrates and nucleic acids.
The lysosomal hydrolases break down complex molecules into simpler, low molecular mass compounds that can be reused. The enzyme content of lysosomes varies in different tissues according to the needs of the tissue.
Lysosomes are not just involved in breaking down material arriving via endocytosis, but also degrade intracellular debris, such as defective organelles and macromolecules. Molecules destined to be degraded are tagged (most frequently by ubiquitination) and then taken up by lysosomes, or are first encapsulated within endosomes that fuse with lysosomes. This process is called autophagy. Products of lysosomal degradation are released from lysosomes into the cytosol and are re-used by the cell. Material that cannot be digested accumulates in vesicles called residual bodies, whose contents are removed from the cell by exocytosis. Some residual bodies contain high concentrations of heterogenous pigmented substances, including polyunsaturated fatty acids and proteins, called lipofucsin or ‘age pigment’. Under particular conditions some lysosomal enzymes are secreted from the cell for the digestion of extracellular material in connective tissue.
What do you suppose is the consequence of a genetic deficiency in individual lysosomal enzymes?
People who are genetically deficient in lysosomal enzymes are unable to break down particular macromolecules that have been directed to the lysosome for recycling. The macromolecules accumulate in the cell, or they may be released to accumulate in the extracellular space.
The deficiencies result in so-called ‘lysosomal storage diseases’. What accumulates depends on which type of enzyme is deficient. For example, the lack of some endoglycosidases leads to the accumulation of heparan sulfate-containing glycoproteins. As a consequence the undegraded molecules accumulate in tissues and cause damage, particularly in the brain where they produce loss of neurons and progressive dementia. Most of these conditions are rare but extremely serious, and affected individuals often die in childhood (Figure 39).