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EMBO reports 7, 4, 390–396 (2006)
doi:10.1038/sj.embor.7400620 AOP Published online: 13 January 2006
Ca2+ shuttling between endoplasmic reticulum and mitochondria underlying Ca2+ oscillations
Kiyoaki Ishii1, Kenzo Hirose1, 2 & Masamitsu Iino1
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1 Department of Pharmacology, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan
2 Department of Cell Physiology, Nagoya University Graduate School of Medicine, Showa-Ku, Nagoya 466-8550, Japan
To whom correspondence should be addressed
Masamitsu Iino Tel: +81 3 5841 3417; Fax: +81 3 5841 3390; E-mail: iino@m.u-tokyo.ac.jp
Received 20 June 2005; Accepted 30 November 2005; Published online 13 January 2006.
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Abstract
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.
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