Chapter 5 Role of lysosomes in cell injury

Lysosomes are acidic intracellular vacuoles of heterogeneous shape, size, and content. Lysosomes contain hydrolytic enzymes that degrade proteins, lipids, carbohydrates, and nucleic acids derived from intracellular (through autophagy) and extracellular (through heterophagy) sources. Lysosomal degradation regulates several physiological cell functions. These include turnover of cellular organelles and extracellular constituents; amino acid and glucose homeostasis; processing of proteins; lipid metabolism; cell growth, differentiation, and involution; host defenses against microorganisms and other pathogens; and removal of necrotic and foreign material from the circulation and from tissues. Lysosomal degradation also plays an important role in the pathophysiology of acute and chronic cell injury, inflammation and repair, and tumor growth and metastasis. The participation of the lysosomes in the specific types of cell injury we have discussed is due to altered regulation of one or more of the following processes: turnover of cellular organelles by autophagic degradation; levels and activities of lysosomal hydrolases; levels of intracellular and extracellular lysosomal hydrolase inhibitors; transport of degradation products from the lysosomal matrix to the cytosol; permeability of the lysosomal membrane to hydrolases; lysosomal vacuolar acidification; transport of degradable substrates and of pathogens to the lysosomes; transport and processing of secretory proteins and lysosomal hydrolases during biogenesis; traffic and fusion of lysosomal vacuoles and vesicles; secretion of lysosomal hydrolases; and accumulation of metals, particularly iron, acidotropic agents, and undegraded and/or undegradable materials in lysosomes.