Mitochondrial Fusion and Fission in Neuronal Death Induced by Cerebral Ischemia-Reperfusion and Its Clinical Application: A Mini-Review

Abstract

Mitochondria are highly dynamic organelles which are joined by mitochondrial fusion and divided by mitochondrial fission. The balance of mitochondrial fusion and fission plays a critical role in maintaining the normal function of neurons, of which the processes are both mediated by several proteins activated by external stimulation. Cerebral ischemia-reperfusion (I/R) injury can disrupt the balance of mitochondrial fusion and fission through regulating the expression and post-translation modification of fusion- and fission-related proteins, thereby destroying homeostasis of the intracellular environment and causing neuronal death. Furthermore, human intervention in fusion- and fission-related proteins can influence the function of neurons and change the outcomes of cerebral I/R injury. In recent years, researchers have found that mitochondrial dysfunction was one of the main factors involved in I/R, and mitochondria is an attractive target in I/R neuroprotection. Therefore, mitochondrial-targeted therapy of the nervous system for I/R gradually started from basic study to clinical application. In the present review, we highlight recent progress in mitochondria fusion and fission in neuronal death induced by cerebral I/R to help understanding the regulatory factors and signaling networks of aberrant mitochondrial fusion and fission contributing to neuronal death during I/R, as well as the potential neuroprotective therapeutics targeting mitochondrial dynamics, which may help clinical treatment and development of relevant dugs.

Smac/DIABLO can predict postoperative delirium in elderly patients after cardiac surgery : A prospective nested case-control study

“…Mitochondrial-targeted therapy of the nervous system gradually started from fundamental study to clinical application. Several novel therapeutic agents, such as cyclosporine A, Nicorandilan, and Mitochondrial calcium uniporter (MUC) by adjust the mitochondrion channel, reducing oxidative stress and Ca2+ overload, inhibiting ROS burst, protect nerve cells [34,35]. Further researches on these mitochondrial-targeted drugs might provide an available strategy for future POD treatment.…”

Effect of Fluoride on Cytotoxicity Involved in Mitochondrial Dysfunction: A Review of Mechanism

“…Fluoride stimulation lead to the increased mRNA expression levels of Cyt C, Caspase-9 and Caspase-3 in a dose-dependent manner, especially in 100 mg/L. Moreover, NaF significantly decreased the level of fission protein and increased the level of fusion protein in the hippocampus of offspring rats, suggesting that fluoride can induce mitochondrial fission / fusion imbalance ( 49 , 50 ). Once the division / fusion balance is disturbed, the mitochondria will undergo morphological and functional changes.…”

Mitochondria at Work: New Insights into Regulation and Dysregulation of Cellular Energy Supply and Metabolism

“…MitoQ can cross the blood brain barrier and cellular membranes in the mitochondria and is considered to activate the Nrf2/ARE pathway leading to an increase in the expression of antioxidant enzymes. Edaravone is a free radical scavenger [ 88 ].…”