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Fuente Pérez, Sergio De La 2025-09-16T12:23:36Z 2025-09-16T12:23:36Z 2019 De la Fuente S, Sheu SS. SR-mitochondria communication in adult cardiomyocytes: A close relationship where the Ca2+ has a lot to say. Arch Biochem Biophys. 2019 Mar 15;663:259-268. doi: 10.1016/j.abb.2019.01.026. Epub 2019 Jan 24. PMID: 30685253; PMCID: PMC6377816. 0003-9861 https://uvadoc.uva.es/handle/10324/77795 10.1016/j.abb.2019.01.026 259 268 Archives of Biochemistry and Biophysics 663 In adult cardiomyocytes, T-tubules, junctional sarcoplasmic reticulum (jSR), and mitochondria juxtapose each other and form a unique and highly repetitive functional structure along the cell. The close apposition between jSR and mitochondria creates high Ca2+ microdomains at the contact sites, increasing the efficiency of the excitation-contraction-bioenergetics coupling, where the Ca2+ transfer from SR to mitochondria plays a critical role. The SR-mitochondria contacts are established through protein tethers, with mitofusin 2 the most studied SR-mitochondrial "bridge", albeit controversial. Mitochondrial Ca2+ uptake is further optimized with the mitochondrial Ca2+ uniporter preferentially localized in the jSR-mitochondria contact sites and the mitochondrial Na+/Ca2+ exchanger localized away from these sites. Despite all these unique features facilitating the privileged transport of Ca2+ from SR to mitochondria in adult cardiomyocytes, the question remains whether mitochondrial Ca2+ concentrations oscillate in synchronicity with cytosolic Ca2+ transients during heartbeats. Proper Ca2+ transfer controls not only the process of mitochondrial bioenergetics, but also of mitochondria-mediated cell death, autophagy/mitophagy, mitochondrial fusion/fission dynamics, reactive oxygen species generation, and redox signaling, among others. Our review focuses specifically on Ca2+ signaling between SR and mitochondria in adult cardiomyocytes. We discuss the physiological and pathological implications of this SR-mitochondrial Ca2+ signaling, research gaps, and future trends spa info:eu-repo/semantics/openAccess SR-mitochondria communication in adult cardiomyocytes: A close relationship where the Ca2+ has a lot to say info:eu-repo/semantics/article