Fig. 6.

Proposed model for the relationships between lysosomal membrane permeabilization (LMP)-dependent and mitochondrial outer membrane permeabilization (MOMP)-dependent cell death pathways in A549 cells exposed to the lower and the higher doses of 58 nm amino-modified polystyrene nanoparticles (PS-NH₂ nanoparticles). In the first case (25 µg mL⁻¹), the internalization of PS-NH₂ nanoparticles results in reactive oxygen species (ROS) production and accumulation of nanoparticles in lysosomes, which activates the LMP-dependent cell death pathway. Both LMP and ROS production can contribute to the induction of MOMP. As the last step in the initiation of the LMP-dependent pathway, the release of mitochondrial contents initiates the oxidative burst, which cause ultimately cell death. The application of the higher dose of nanoparticles (100 µg mL⁻¹), in addition to the abovementioned process, the MOMP-dependent pathway can be triggered directly, i.e. independently of LMP and ROS, thus inducing an oxidative burst which is followed by LMP. The LMP- and MOMP-dependent pathways converge in the execution phase to activate caspase 3/7 and the phosphatidylserine flip to the outer membrane, and finally lead to cell death