Mitochondrial dysfunction - Silent killer in cerebral ischemia.
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.
Sri Ramachandra University, No. 1, Ramachandra Nagar, Porur, Chennai, Tamil Nadu, India. Electronic address: qamanagerceft@sriramachandra.edu.in.
Pramila
P
Bakthavachalam
Department of Biochemistry and Molecular Biology, Health Sciences Center-Shreveport, Louisiana State University, Louisiana, USA.
Prakash Srinivasan Timiri
PST
Shanmugam
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D002545:Brain Ischemia / Q000209:etiology* / Q000473:pathology*; D002118:Calcium / Q000378:metabolism; D006801:Humans; D008928:Mitochondria / Q000473:pathology; D028361:Mitochondrial Diseases / Q000150:complications*; D009474:Neurons / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D018384:Oxidative Stress / Q000502:physiology; D017382:Reactive Oxygen Species / Q000378:metabolism
D017382:Reactive Oxygen Species; D002118:Calcium
Cerebral ischemia; Excitotoxicity; Mitochondrial transition pore; Mitophagy