*6.3.3. Lysosomes*

Lysosomes are organelles that contain acidic hydrolases such as cathepsins. Rupture of lysosomes release cathepsins to the cytosol, where they can trigger apoptosis or necrosis. Cystatins, on the other hand, are cytosolic proteins that act as negative regulators of cathepsins when they are translocated from lysosomes to the cytosol. Apoptosis initiated in lysosomes follows a mitochondrion-dependent pathway associated to caspase activation. However, it has been shown that cathepsin D activates Bax and AIF release, triggering a caspase-independent apoptotic pathway [37]. Furthermore, some cathepsins induce Bid cleavage [38], interaction with Bcl-2 proteins and permeabilization of the mitochondrial membrane [64]. In addition, cathepsins can alter mitochondria functions by cleaving subunits of the oxidative phosphorylation complexes, inducing ROS generation [12]. Lysosomes are essentially involved in **autophagic cell death** mechanisms.
