Biology of the lysosome

Lysosomes are the cell’s main degradative compartment for complex macromolecules as well as intracellular structures (like mitochondria or parts of cell membrane, Golgi or ER). Optimal degradation of all kinds of materials involves a set of more than thirty different lysosomal enzymes (acid hydrolases), which are most active in a very acidic environment (low pH). However, a number of lysosomal membrane proteins are also critical as they are responsible for transport into and out of the lysosome as well as interactions with the rest of the cell’s interior.

Lysosomes represent just one end of the spectrum of vesicles represented in the endosomal-lysosomal compartment.

Primary lysosome; small (50 nm) vesicle carrying lysosomal membrane proteins as well as lysosomal pro-enzymes bound to mannose-6-phosphate receptors (MPRs)

Early endosome; 200-800 nm-sized vesicle resulting from the fusion of primary lysosomes with vesicles containing ingested materials (through endocytosis) or engulfed intracellular structures (autophagosomes)

Late endosome or multivesicular body; vesicle containing smaller vesicles either with materials destined for degradation or for exocytosis (exosomes)

Hybrid organelle; fusion product of multivesicular body and lysosome

Lysosomes (with low pH allowing optimal enzyme activities)

In non-dividing, long-lived cells there probably is little biogenesis of new lysosomes, but the already present lysosomes are in a process of highly dynamic remodeling (as a result of various kinds of vesicle-vesicle interactions). On average, a non-dividing, long-lived cell has about 300 lysosomes accounting - in total - for less than 1% of total cell volume.

Tagging of lysosomal pro-enzymes with mannose-6-phosphate groups is critical for their mannose-6-phosphate receptor (MPR) mediated transport to the endosomal-lysosomal compartment. For lysosomal pro-enzymes lost from the cell a similar MPR-mediated endocytosis can serve as a ‘rescue’ route. Receptor-mediated uptake followed by delivery to the endosomal-lysosomal compartment actually is the basis for intravenous enzyme replacement therapies now available for various LSDs.

The lysosome is not simply a waste deposit, which would not cause any problems until it becomes tremendously oversized, but actually is critical in a variety of cellular processes. See Lysosomes and disease.