Zn 2+ , mitochondria and neuronal injury

Zn 2+ critically contributes to the neural injury observed in epilepsy and transient global ischaemia. Mechanisms by which Zn 2+ exerts its potent neurotoxic effects are still largely unknown. We have recently suggested that an important factor could be Zn 2+ dependent disruption of mitochondrial function. As in the case of Ca 2+ , neuronal mitochondria take up Zn 2+ to restore Zn 2+ i homeostasis. However, mitochondrial Zn 2+ sequestration leads to potent mitochondrial dysfunction with prolonged loss of mitochondrial membrane potential and free radicals generation. Intriguingly, in direct comparison to Ca 2+ , Zn 2+ seems to induce these effects with a considerably greater degree of potency. These injurious, and likely necrotic, effects are particularly evident upon large (micromolar) Zn 2+ i rises. Conversely, submicromolar [Zn 2+ ] i increases promote release of pro‐apoptotic factors, suggesting that different degrees of cytosolic [Zn 2+ ] i rises might activate distinct injurious pathways.