Model of compound accumulation and autophagy perturbation.

<p>Basic lipophilic compounds (B) pass through cell membranes and enter lysosomes. The acidic environment within the lysosome causes the majority of the compounds to become protonated (BH) and trapped. Compound accumulation can induce lysosome membrane permeablization and cause cell death. Concurrently, lysosomal dysfunction can potentially occur from a decrease of lysosomal enzyme activity due to either pH changes or direct enzymatic interactions. As a result, the autophagy process could be hindered. An increase of SQSTM1/p62 resulting from autophagy inhibition could further modulate activity of the Nrf2 signaling pathway.