However, mitochondrial Ca2+ uptake has great repercussions on cardiomyocytes fate; in healthy bodies, by ensuring bioenergetics and cardiac contractility [9,10,176], and in disease bodies, where an overload can induce the PTPC opening upon I/R and a vicious cycling of ROS generation, oxidation of RyR2, and SR Ca2+ leak in HF, associated with mitochondrial fragmentation and dysfunction [177]. The gene discussed is RYR2; the disease is hydrops fetalis.