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Ca2+ shuttling between endoplasmic reticulum and mitochondria underlying Ca2+ oscillations
Kiyoaki Ishii1, Kenzo Hirose, Masamitsu Iino
1Department of Pharmacology, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Japan.
EMBO Reports
|January 18, 2006
Summary
Calcium (Ca2+) oscillations are crucial for cell function. This study reveals that Ca2+ shuttling between the endoplasmic reticulum and mitochondria acts as the pacemaker mechanism driving these essential cellular oscillations.
Area of Science:
- Cell Biology
- Calcium Signaling
Background:
- Cellular functions are regulated by calcium (Ca2+) oscillations, involving cyclic release from intracellular stores.
- The precise pacemaker mechanism underlying Ca2+ oscillations remains incompletely understood.
Purpose of the Study:
- To elucidate the pacemaker mechanism of Ca2+ oscillations.
- To investigate the role of intracellular Ca2+ stores, specifically the endoplasmic reticulum (ER) and mitochondria, in generating Ca2+ oscillations.
Main Methods:
- Utilized green fluorescent protein-based Ca2+ indicators targeted to the ER and mitochondria.
- Monitored Ca2+ dynamics within these organelles during agonist stimulation.
Main Results:
- Observed Ca2+ shuttling between the ER and mitochondria synchronized with Ca2+ oscillations.
- Demonstrated that mitochondrial Ca2+ release, mediated by the Na+/Ca2+ exchanger, triggers subsequent ER Ca2+ release and oscillation peaks.
- Showed this cycle repeats until mitochondrial Ca2+ is depleted.
Conclusions:
- Ca2+ shuttling between the ER and mitochondria plays a critical pacemaker role in the generation of Ca2+ oscillations.
- This ER-mitochondria crosstalk is fundamental to the oscillatory release of intracellular calcium.