Mitochondria-associated membrane-modulated Ca2+ transfer: A potential treatment target in cardiac ischemia reperfusion injury and heart failure

Effective Ca2+ dependent mitochondrial energy supply is imperative for proper cardiac contractile activity, while disruption of Ca2+ homeostasis participates in the pathogenesis of multiple human diseases. This phenomenon is particularly prominent in cardiac ischemia and reperfusion (I/R) and heart failure, both of which require strict clinical intervention. The interface between endoplasmic reticula (ER) and mitochondria, designated the mitochondria-associated membrane (MAM), is now regarded as a crucial mediator of Ca2+ transportation. Thus, interventions targeting this physical and functional coupling between mitochondria and the ER are highly desirable. Increasing evidence supports the notion that restoration, and maintenance, of the physiological contact between these two organelles can improve mitochondrial function, while inhibiting cell death, thereby sufficiently ameliorating I/R injury and heart failure development. A better understanding regarding the underlying mechanism of MAM-mediated transport will pave the way for identification of novel treatment approaches for heart disease. Therefore, in this review, we summarize the crucial functions and potential mechanisms of MAMs in the pathogenesis of I/R and heart failure.

Automated summary

The mitochondria-associated membrane (MAM) plays a crucial role in the pathogenesis of cardiac ischemia and reperfusion (I/R) and heart failure. Restoring and maintaining the physiological contact between mitochondria and the endoplasmic reticulum (ER) may improve mitochondrial function, inhibit cell death, and alleviate heart injury and disease development.