Roles of mitochondrial dynamics modulators in cardiac ischaemia/reperfusion injury

Abstract

The current therapeutic strategy for the management of acute myocardial infarction (AMI) is to return blood flow into the occluded coronary artery of the heart, a process defined as reperfusion. However, reperfusion itself can increase mortality rates in AMI patients because of cardiac tissue damage and dysfunction, which is termed ‘ischaemia/reperfusion (I/R) injury’. Mitochondria play an important role in myocardial I/R injury as disturbance of mitochondrial dynamics, especially excessive mitochondrial fission, is a predominant cause of cardiac dysfunction. Therefore, pharmacological intervention and therapeutic strategies which modulate the mitochondrial dynamics balance during I/R injury could exert great beneficial effects to the I/R heart. This review comprehensively summarizes and discusses the effects of mitochondrial fission inhibitors as well as mitochondrial fusion promoters on cardiac and mitochondrial function during myocardial I/R injury. The comparison of the effects of both compounds given at different time‐points during the course of I/R injury (i.e. prior to ischaemia, during ischaemia and at the reperfusion period) are also summarized and discussed. Finally, this review also details important information which may contribute to clinical practices using these drugs to improve the quality of life in AMI patients.

Identification of novel dynamin‐related protein 1 (Drp1) GTPase inhibitors: Therapeutic potential of Drpitor1 and Drpitor1a in cancer and cardiac ischemia‐reperfusion injury

“…PAH and lung cancer share many similarities including a hyperproliferative and apoptosis-resistant phenotype. 21 We have shown previously that there is a basal fragmentation of mitochondria in RV myocytes of monocrotaline rats with pulmonary arterial hypertension (PAH), even in the absence of induced IR. Previous studies have explored the concept that dysregulated mitochondrial dynamics caused by increased activity of the fission mediator Drp1, contributing to the hyperproliferative phenotype of cancer and PAH cells.…”

“…Identification of 17 candidate Drp1 inhibitors through screening of a proprietary chemical compound library of over 4 000 compounds using in silico analysis. 21 Inhibition of Drp1 activity or the interaction between Drp1 and its binding partner Fis1 is cardioprotective during experimental IR. Mitochondrial fission and cell cycle progression are highly coordinated, which ensures equitable distribution of mitochondria to daughter cells.…”

Melatonin attenuates myocardial ischemia‐reperfusion injury via improving mitochondrial fusion/mitophagy and activating the AMPK‐OPA1 signaling pathways

“…In contrast to mitochondrial fission, mitochondrial fusion promotes communication between mitochondria, repressing the formation of mitochondrial fragmentation and sustaining mitochondrial genomic homeostasis . Moreover, mitochondrial fusion enhances the activity of mitophagy, and the latter is an evolutionally conserved catabolic pathway that clears damaged mitochondrial fragmentation . Thus, cells with well‐orchestrated mitochondrial fusion and mitophagy are able to sequester dysfunctional mitochondria .…”

High‐Saturated Fat High‐Sugar Diet Accelerates Left‐Ventricular Dysfunction Faster than High‐Saturated Fat Diet Alone via Increasing Oxidative Stress and Apoptosis in Obese‐Insulin Resistant Rats

“…Mitochondrial fission is mainly regulated by dynamin related protein 1 (Drp1) . Drp1 mostly resides in the cytosol, and can be translocated to mitochondria by phosphorylation at Ser616 site . Mitochondrial fusion process is controlled by mitofusin2 (Mfn2) to regulate mitochondrial membrane fusion .…”