Role of lysosomes in programmed cell death pathways

Lysosomes help programmed cell death (apoptosis) by releasing cathepsins that activate caspases, degrade organelles, and amplify mitochondrial death signals.

Mechanistic role

• Lysosomal membrane permeabilization (LMP): Controlled permeabilization releases limited cathepsins into cytosol.
• Caspase activation: Cathepsins can activate caspase-8 and -9, triggering apoptosis cascades.
• Mitochondrial crosstalk: Lysosomal enzymes promote release of cytochrome c from mitochondria, enhancing apoptosis.
• Autophagy-apoptosis balance: Lysosomes regulate autophagy, which can delay or promote apoptosis depending on context.

Examples

• During immune cell selection, lysosomes assist in eliminating defective T-cells.
• Cancer therapy drugs often induce LMP to kill tumor cells.