Calcium (Ca2+) is a divalent cation and a universal second messenger that regulates the most important functions and facets of all eukaryotic cells, including: gene expression, proliferation, regulation of bioenergetics, contraction of muscles, mediation of fertilization, and many other cellular functions. Regulation of free intracellular concentration of Ca2+ is an important mechanism for intracellular signaling, and it is a key component in the mediation of many cell functions and biochemical reactions, being crucial for signal transduction in cells. On top of all that, intra-mitochondrial Ca2+ regulates a cascade of physiological and pathophysiological processes in cells The normal level of intra-mitochondrial Са2+ is essential for the correct functioning of mitochondria; whereas Ca2+ overload is typical for a wide range of mitochondrial dysfunctions and pathophysiological processes. Homeostasis of Ca2+ in the mitochondria is determined by the delicate balance of mitochondrial Ca2+ transport systems in both the inner (IMM) and outer mitochondrial membrane (OMM). Ca2+ influx and efflux systems are composed of different components, including: channels, pumps, antiporters, or Ca2+ binding proteins that cooperate to maintain intra-mitochondrial Ca2+ homeostasis.

Calcium (Ca2+) is a divalent cation and a universal second messenger that regulates the most important functions and facets of all eukaryotic cells, including: gene expression, proliferation, regulation of bioenergetics, contraction of muscles, mediation of fertilization, and many other cellular functions [1–5]. Regulation of free intracellular concentration of Ca2+ is an important mechanism for intracellular signaling, and it is a key component in the mediation of many cell functions and biochemical reactions, being crucial for signal transduction in cells [2,6–10]. On top of all that, intra-mitochondrial Ca2+ regulates a cascade of physiological and pathophysiological processes in cells [10–15]. The normal level of intra-mitochondrial Са2+ is essential for the correct functioning of mitochondria; whereas Ca2+ overload is typical for a wide range of mitochondrial dysfunctions and pathophysiological processes [14,15,37,39,41]. Homeostasis of Ca2+ in the mitochondria is determined by the delicate balance of mitochondrial Ca2+ transport systems in both the inner (IMM) and outer mitochondrial membrane (OMM). Ca2+ influx and efflux systems are composed of different components, including: channels, pumps, antiporters, or Ca2+ binding proteins that cooperate to maintain intra-mitochondrial Ca2+ homeostasis [10,14,38,39,42].