Abstract
Zinc plays an important role in cardiomyocytes, where it exists in bound and histochemically reactive labile Zn(2+) forms. Although Zn(2+) concentration is under tight control through several Zn(2+)-transporters, its concentration and intracellular distribution may vary during normal cardiac function and pathological conditions, when the protein levels and efficacy of Zn(2+) transporters can lead to zinc re-distribution among organelles in cardiomyocytes. Such dysregulation of cellular Zn(2+) homeostasis leads to mitochondrial and ER stresses, and interrupts normal ER/mitochondria cross-talk and mitophagy, which subsequently, result in increased ROS production and dysregulated metabolic function. Besides cardiac structural and functional defects, insufficient Zn(2+) supply was associated with heart development abnormalities, induction and progression of cardiovascular diseases, resulting in accelerated cardiac ageing. In the present review, we summarize the recently identified connections between cellular and mitochondrial Zn(2+) homeostasis, ER stress and mitophagy in heart development, excitation-contraction coupling, heart failure and ischemia/reperfusion injury. Additionally, we discuss the role of Zn(2+) in accelerated heart ageing and ageing-associated rise of mitochondrial ROS and cardiomyocyte dysfunction.