Cardiac dysfunction is a complex clinical syndrome, and some cross-sectional clinical studies on this topic have shown the role of zinc deficiencies on the pathogenesis of heart failure, at most, consequent to increase oxidative stress [1], [2], [3]. In this regard, we, previously, have shown the important contribution of increased free Zn2+ levels ([Zn2+]) in cardiomyocytes, and alterations in some Zn2+-transporters such as ZIP7 and ZnT7 in heart samples from patients with either dilated or ischemic cardiomyopathy or from experimental animals. Also, it has been shown the localizations and the role of two Zn2+-transporters, ZIP7 and ZnT7 in ventricular cardiomyocytes from diabetic rats [4]. Furthermore, the localization of ZnT7 into the mitochondria has been demonstrated with the increased ZnT7 level in isolated mitochondria under hyperglycemic- or doxorubicin-treated cardiomyocytes, which are further affecting S(E)R-mitochondria coupling in cardiomyocytes under pathological conditions [5]. A supporting study demonstrated an essential function of ZnT7 in dietary zinc absorption and regulation of body adiposity by using Znt7(Slc30a7)-deficient mice [6], [7].

Zinc is an important micronutrient in the diet of mammalians whereas its deficiency seems to have an association with some diseases such as diabetes mellitus. However, our studies as well as others have shown some contradictory results related to the changes in protein expression levels and functions of Zn2+ transporters, particularly under pathological stimuli. Here, taking into consideration the possible role of ZnT7 as a pivotal factor in the regulation of Zn2+-homeostasis in cardiomyocytes localized into not sarco(endo)plasmic reticulum S(E)R but also the mitochondria, we focused to demonstrate how an increased expression level of ZnT7 in cardiomyocytes can coordinate first [Zn2+]i and second the mitochondria function via regulation of not only [Zn2+]Mit but also [Ca2+]Mit in hyperinsulinemic cells. In the present study, we have shown the important role of ZnT7 in the regulation of mitochondria function via not only the control of [Zn2+]Mit but also epigenetic regulation in cardiomyocytes through histone modification.