Fig. 4. Schematic representation of the mitochondrial membrane: different NP surface charges induce different mechanisms of cell death.⁷⁷ The neutrally charged NP (*) does not disrupt the mitochondrial membrane potential, and therefore apoptosis is not activated. The positively charged NP (+) disrupts the slight negative charge on the cytosolic side of the outer membrane, leading to a disruption in the mitochondrial membrane potential. The disruption damages the membrane and proteins, such as caspase activators, leak into the cytosol. The negatively charged NP (−) increases the negative charge on the outer membrane, which leads to a disruption in the mitochondrial membrane potential. The mitochondria compensate by releasing calcium ions that were stored in the matrix of the mitochondria. The spike in calcium induced apoptosis.⁷⁷.