Figure 1.

From lysosomal membrane permeabilization (LMP) to cell death through mitochondrial outer membrane permeabilization (MOMP). LMP is a process in which intralysosomal content (mostly cathepsins but also ROS) is leaked to the cytoplasm. Massive disruption of lysosomes induces cell death by necrosis, but selective LMP can induce apoptosis by MOMP. Cathepsins can promote, on the one hand, the cleavage of the pro-apoptotic protein Bid; and on the other hand, the translocation of Bcl-2-associated killer (BAK) and BAX to the outer mitochondrial membrane (OMM) where they form pores. Truncated Bid (tBid) can itself form pores to the OMM but can also activate BAK/BAX. These two processes can induce apoptosis, via release of cytocrome c and in a caspase-dependent way or independently of caspases. A positive feedback loop exists given that caspases and cathepsins are also inducers of LMP.