The role of labile Zn2+ and Zn2+-transporters in the pathophysiology of mitochondria dysfunction in cardiomyocytes.

An important energy supplier of cardiomyocytes is mitochondria, similar to other mammalian cells. Studies have demonstrated that any defect in the normal processes controlled by mitochondria can lead to abnormal ROS production, thereby high oxidative stress as well as lack of ATP. Taken into consideration, the relationship between mitochondrial dysfunction and overproduction of ROS as well as the relation between increased ROS and high-level release of intracellular labile Zn2+, those bring into consideration the importance of the events related with those stimuli in cardiomyocytes responsible from cellular Zn2+-homeostasis and responsible Zn2+-transporters associated with the Zn2+-homeostasis and Zn2+-signaling. Zn2+-signaling, controlled by cellular Zn2+-homeostatic mechanisms, is regulated with intracellular labile Zn2+ levels, which are controlled, especially, with the two Zn2+-transporter families; ZIPs and ZnTs. Our experimental studies in mammalian cardiomyocytes and human heart tissue showed that Zn2+-transporters localizes to mitochondria besides sarco(endo)plasmic reticulum and Golgi under physiological condition. The protein levels as well as functions of those transporters can re-distribute under pathological conditions, therefore, they can interplay among organelles in cardiomyocytes to adjust a proper intracellular labile Zn2+ level. In the present review, we aimed to summarize the already known Zn2+-transporters localize to mitochondria and function to stabilize not only the cellular Zn2+ level but also cellular oxidative stress status. In conclusion, one can propose that a detailed understanding of cellular Zn2+-homeostasis and Zn2+-signaling through mitochondria may emphasize the importance of new mitochondria-targeting agents for prevention and/or therapy of cardiovascular dysfunction in humans.