Lysosomes

Lysosomes are membrane-bound organelles found in most animal cells that function as the cell’s intracellular digestive system. They contain a variety of acid hydrolases—enzymes that break down proteins, lipids, nucleic acids, and carbohydrates—and maintain an acidic internal pH of about 4.5 to 5.0. The lysosomal membrane protects the cytosol from these enzymes and houses proton pumps and transporters that preserve acidity and enable metabolite export.

Most lysosomal enzymes are synthesized in the endoplasmic reticulum and tagged with mannose-6-phosphate in the Golgi apparatus for delivery to lysosomes. They reach the organelle via M6P receptors and vesicular trafficking. Lysosomes originate from late endosomes and mature by fusion and remodeling; some are formed de novo.

Functions include digestion of material taken up by endocytosis, phagocytosis, and autophagy, as well as degradation and recycling of damaged organelles. In autophagy, autophagosomes fuse with lysosomes to form autolysosomes, where contents are degraded and metabolites returned to the cytosol for reuse. Lysosomes also participate in nutrient sensing and signaling, with roles linked to the mTOR pathway and transcription factors such as TFEB that regulate lysosome biogenesis.

Defects in lysosomal enzymes or trafficking cause lysosomal storage diseases, such as Pompe disease, Gaucher disease, Niemann-Pick disease, and mucolipidosis. These disorders result in substrate accumulation and progressive cellular dysfunction.

Lysosomes were first described as cellular organelles by Christian de Duve in the 1950s.