Mitochondria, sodium, and calcium in neuronal dysfunction

Abstract

Neuronal mitochondria in situ respond to changes in their cytoplasmic ionic environment. When calcium rises above 500 nM, the organelles accumulate the cation. This is an energy-requiring process and calcium overload can lead to the mitochondrial permeability transition and cell necrosis. Increases in cytoplasmic sodium indirectly affect mitochondrial bioenergetics by activating the plasma membrane sodium-potassium ATPase, increasing ATP demand and affecting mitochondrial Ca2+ cycling. Each factor comes into play during glutamate excitotoxicity, which is caused by pathological NMDA receptor activation; excitotoxicity is firmly implicated in neuronal damage after stroke and is implicated in a wide range of neurodegenerative disorders. The danger of oxidative stress may lie primarily in decreasing the capacity of mitochondria to respond to these ATP demands.