Ca2+ shuttling between endoplasmic reticulum and mitochondria underlying Ca2+ oscillations

• Published in: EMBO reports Vol. 7; no. 4; pp. 390 - 396
• Main Authors: Ishii, Kiyoaki, Hirose, Kenzo, Iino, Masamitsu
• Format: Journal Article
• Language: English
• Published: Chichester, UK John Wiley & Sons, Ltd 01-04-2006; Blackwell Publishing Ltd
• Subjects: Calcium; Calcium - chemistry; Calcium - metabolism; calcium oscillation; Calcium Signaling; Cations, Divalent - chemistry; Cellular biology; Cytosol - metabolism; endoplasmic reticulum; Endoplasmic Reticulum - metabolism; GFP; HeLa Cells; Humans; imaging; mitochondria; Mitochondria - metabolism; Models, Biological; Scientific Report
• ISSN: 1469-221X; 1469-3178
• DOI: 10.1038/sj.embor.7400620

Although many cell functions are regulated by Ca2+ oscillations induced by a cyclic release of Ca2+ from intracellular Ca2+ stores, the pacemaker mechanism of Ca2+ oscillations remains to be explained. Using green fluorescent protein‐based Ca2+ indicators that are targeted to intracellular Ca2+ stores, the endoplasmic reticulum (ER) and mitochondria, we found that Ca2+ shuttles between the ER and mitochondria in phase with Ca2+ oscillations. Following agonist stimulation, Ca2+ release from the ER generated the first Ca2+ oscillation and loaded mitochondria with Ca2+. Before the second Ca2+ oscillation, Ca2+ release from the mitochondria by means of the Na+/Ca2+ exchanger caused a gradual increase in cytoplasmic Ca2+ concentration, inducing a regenerative ER Ca2+ release, which generated the peak of Ca2+ oscillation and partially reloaded the mitochondria. This sequence of events was repeated until mitochondrial Ca2+ was depleted. Thus, Ca2+ shuttling between the ER and mitochondria may have a pacemaker role in the generation of Ca2+ oscillations.