Toxic effects induced by TiO2 NPs in H9c2 cells. TiO2 NPs are internalized into the cytoplasm (1), producing strong oxidative stress and changes in the cellular redox state, increasing ROS production and mitochondrial damage (2), decreasing mitochondrial membrane potential (ΔΨm) (3). High oxidative stress causes strong cell damage, associated with autophagy (4), involving the formation of autophagosomes in the endoplasmic reticulum (ER), these in turn fuse with lysosomes to produce degradation of cytoplasmic components formed during cell damage. Finally, TiO2 NPs increase membrane permeability and induce necrosis (5).