Lysosome

Lysosome (e) (from Greek lysis = solution, and soma = body) are 0.1-1.1 μm large, membrane-enclosed organelles, which are detectable in the cytoplasm of all nucleated cells. The lysosomal membrane has specific features. On the inside of this biomembrane, the membrane proteins are highly glycosylated to protect the cytosol from the encapsulated enzymes.

The lysosomes contain numerous hydrolyzing enzymes such as proteases, nucleases and lipases. These only achieve a high biological activity in an acidic environment (pH<5). This ensures that enzymes that enter the cytosol from damaged lysosomes cannot degrade essential cellular components.

In the cytoplasm the so-called primary lysosomes fuse with endocytotic vesicles or phagosomes to form so-called secondary lysosomes. Lysosomes are found in particularly large quantities in the cytoplasm of antigen-presenting cells (phagolysosomes). Lysosomes also contain various antimicrobially active substances as well as components of some receptors (neutrophil granules).

Degradation of biopolymers: The most important function of lysosomes is to break down biopolymers foreign to the cell (heterophagy) into their monomers. Lysosomes also digest the cell's own material (autophagy), an enzymatic process that is converted during apoptosis. A further task of the lysosome is the storage and degradation of cell toxins. By storing the harmful substances in their vesicles, the lysosomes can prevent direct toxic effects on the cell.

Lysosomes and drugs: Furthermore, weak bases, which is the case with many drugs, tend to accumulate in the acidic intracellular lysosomal compartments. This mechanism is called "lysosomotropy". Thus, the tissue concentration of lysosomotropic drugs is higher than the actual plasma concentration. Their half-life in tissue is higher than in plasma. Examples are haloperidol, levomepromazine or amantadine.

Lysosomal storage diseases: Defects in lysosomal enzyme functions lead to so-called lysosomal storage diseases of which about 50 different forms are known. The best known are M. Gaucher (E75.21), an autosomal recessive inherited deficiency of glucocerebrosidase, M. Fabry (E75.2), an X-linked deficiency of alpha-galactosidase, M. Pompe, a defect of acid alpha-glucosidase, M. Hurler, a defect in alpha-iduronisadase, etc. In all lysosomal storage diseases, there is an accumulation of non-degradable macromolecules (e.g. glucocerebrosides in Gaucher's disease) in the lysosomes.

Lysosomes and ANCA: Autoantibodies can be formed against some of the lysosomal enzymes of leukocytes (see ANCA).

Lysosomes and disorders of melanin pigmentation: In some rare diseases(Hermansky-Pudlak syndrome, Chediak-Higashi syndrome) organelles related to lysosomes are dysfunctional, e.g. in thrombocytes, macrophages and granulocytes. At the same time the formation, transport or transfer of melanosomes related to lysosomes is disturbed (albinoidism).

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2. Platt FM (2014) Sphingolipid lysosomal storage disorders. Nature 510(7503):68-75.
3. Sardiello M et al.(2009) A gene network regulating lysosomal biogenesis and function. Science. 325(5939):473-437.