Mitochondrial dysfunction - Silent killer in cerebral ischemia

Abstract

Mitochondrial dysfunction aggravates ischemic neuronal injury through activation of various pathophysiological and molecular mechanisms. Ischemic neuronal injury is particularly intensified during reperfusion due to impairment of mitochondrial function. Mitochondrial mutilation instigates alterations in calcium homeostasis in neurons, which plays a pivotal role in the maintenance of normal neuronal function. Increase in intracellular calcium level in mitochondria triggers the opening of mitochondrial transition pore and over production of reactive oxygen species (ROS). Several investigations have concluded that ROS not only contribute to lipids and proteins damage, but also transduce apoptotic signals leading to neuronal death. In addition to the above mentioned reasons, endoplasmic reticulum (ER) stress due to excitotoxicity also leads to neuronal death. Recently, some newer proteins have been claimed to induce "mitophagy" by triggering the receptors on autophagic membranes leading to neurodegeneration. This review summarizes the mechanisms underlying neuronal death involving mitochondrial dysfunction and mitophagy.

Keywords: Cerebral ischemia; Excitotoxicity; Mitochondrial transition pore; Mitophagy.