Another effective means of preventing the mitochondrial spiral is by preventing the initial reactive oxygen species production induced by toxic insults. One such target is the reactive oxygen species production induced by calcium
overload associated with disruption of mitochondrial calcium buffering capabilities, as seen in many neurodegenerative
diseases [139]. Cytoplasmic calcium is normally sequestered within the mitochondrial matrix to aid appropriate
cellular and mitochondrial membrane polarization, but an imbalance in calcium handling can lead to activation
of nitric oxide synthase and generation of reactive oxygen species, which can be prevented by inhibition of calcium uptake through the calcium uniporter [139].