Mitochondrial Quality Control: Role in Cardiac Models of Lethal Ischemia-Reperfusion Injury

• Published in: Cells
• Main Authors: Andrew R. Kulek, Anthony Anzell, Joseph M. Wider, Thomas H. Sanderson, Karin Przyklenk
• Format: Article
• Language: English
• Published: MDPI AG 2020-01-01
• Subjects: heart; ischemia; reperfusion; mitochondria; fission; fusion; mitophagy
• Online Access: https://www.mdpi.com/2073-4409/9/1/214

The current standard of care for acute myocardial infarction or &#8216;heart attack&#8217; is timely restoration of blood flow to the ischemic region of the heart. While reperfusion is essential for the salvage of ischemic myocardium, re-introduction of blood flow paradoxically <i>kills</i> (rather than rescues) a population of previously ischemic cardiomyocytes&#8212;a phenomenon referred to as &#8216;lethal myocardial ischemia-reperfusion (IR) injury&#8217;. There is long-standing and exhaustive evidence that mitochondria are at the nexus of lethal IR injury. However, during the past decade, the paradigm of mitochondria as mediators of IR-induced cardiomyocyte death has been expanded to include the highly orchestrated process of mitochondrial quality control. Our aims in this review are to: (1) briefly summarize the current understanding of the pathogenesis of IR injury, and (2) incorporating landmark data from a broad spectrum of models (including immortalized cells, primary cardiomyocytes and intact hearts), provide a critical discussion of the emerging concept that mitochondrial dynamics and mitophagy (the components of mitochondrial quality control) may contribute to the pathogenesis of cardiomyocyte death in the setting of ischemia-reperfusion.