ABSTRACT
Reactive oxygen species are among the few established mediators of lysosomal membrane permeabilization (LMP). They can be produced in the cell as by-products of mitochondrial respiration or lysosomal degradation of iron-containing proteins. A consequence of LMP is the release of lysosomal contents including soluble enzymes. The activity of these enzymes has an optimum at the acidic pH of the lysosomal lumen. Development of reliable methods to detect LMP has revived the interest in lysosomal cell death. Subsequently, emerging genetic data has corroborated the role of cathepsins as evolutionarily conserved executors of cell death, and lysosomal leakage as a significant mediator of both physiological and pathological cell demise. Lysosome-dependent cell death is evolutionarily conserved from yeast, roundworm and fruit fly to mammalian cells and tissues, and it contributes to numerous physiological processes as well as degenerative, inflammatory and microbial diseases.
