Not only would estradiol-induced regulation of mitochondrial calcium homeostasis protect against cytotoxicity, but increased calcium uptake can also modify basal mitochondrial function. It is now widely accepted that calcium entering mitochondria activates key intramitochondrial enzymes, dehydrogenase activity, and thereby cause increased ATP production [63]. Support for this is evidenced by an increase in succinate dehydrogenase activity in the mitochondrial fraction from the brains of estradiol treated rats [54]. Limited calcium uptake also increases the availability of substrate nucleotides and the rate of electron transport, leading to increased efficiency of oxidative phosphorylation [63]. It has been suggested that these calcium-dependent changes in mitochondrial respiration allow excitable cells to couple ATP production with cellular activity [63], and there is evidence that mitochondria play a role in synaptic plasticity [82].