Title |
The Mitochondrial Na+/Ca2+ Exchanger Upregulates Glucose Dependent Ca2+ Signalling Linked to Insulin Secretion
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Published in |
PLOS ONE, October 2012
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DOI | 10.1371/journal.pone.0046649 |
Pubmed ID | |
Authors |
Iulia I. Nita, Michal Hershfinkel, Daniel Fishman, Eyal Ozeri, Guy A. Rutter, Stefano L. Sensi, Daniel Khananshvili, Eli C. Lewis, Israel Sekler |
Abstract |
Mitochondria mediate dual metabolic and Ca(2+) shuttling activities. While the former is required for Ca(2+) signalling linked to insulin secretion, the role of the latter in β cell function has not been well understood, primarily because the molecular identity of the mitochondrial Ca(2+) transporters were elusive and the selectivity of their inhibitors was questionable. This study focuses on NCLX, the recently discovered mitochondrial Na(+)/Ca(2+) exchanger that is linked to Ca(2+) signalling in MIN6 and primary β cells. Suppression either of NCLX expression, using a siRNA construct (siNCLX) or of its activity, by a dominant negative construct (dnNCLX), enhanced mitochondrial Ca(2+) influx and blocked efflux induced by glucose or by cell depolarization. In addition, NCLX regulated basal, but not glucose-dependent changes, in metabolic rate, mitochondrial membrane potential and mitochondrial resting Ca(2+). Importantly, NCLX controlled the rate and amplitude of cytosolic Ca(2+) changes induced by depolarization or high glucose, indicating that NCLX is a critical and rate limiting component in the cross talk between mitochondrial and plasma membrane Ca(2+) signalling. Finally, knockdown of NCLX expression was followed by a delay in glucose-dependent insulin secretion. These findings suggest that the mitochondrial Na(+)/Ca(2+) exchanger, NCLX, shapes glucose-dependent mitochondrial and cytosolic Ca(2+) signals thereby regulating the temporal pattern of insulin secretion in β cells. |
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Geographical breakdown
Country | Count | As % |
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Unknown | 54 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
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Researcher | 11 | 20% |
Student > Ph. D. Student | 10 | 19% |
Professor | 6 | 11% |
Student > Master | 5 | 9% |
Professor > Associate Professor | 4 | 7% |
Other | 7 | 13% |
Unknown | 11 | 20% |
Readers by discipline | Count | As % |
---|---|---|
Biochemistry, Genetics and Molecular Biology | 14 | 26% |
Agricultural and Biological Sciences | 10 | 19% |
Medicine and Dentistry | 8 | 15% |
Neuroscience | 4 | 7% |
Pharmacology, Toxicology and Pharmaceutical Science | 2 | 4% |
Other | 4 | 7% |
Unknown | 12 | 22% |