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Plos One : the Mitochondrial Na+, Volume 7

By Saks, Valdur

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Book Id: WPLBN0003961249
Format Type: PDF eBook :
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Reproduction Date: 2015

Title: Plos One : the Mitochondrial Na+, Volume 7  
Author: Saks, Valdur
Volume: Volume 7
Language: English
Subject: Journals, Science, Medical Science
Collections: Periodicals: Journal and Magazine Collection
Historic
Publication Date:
Publisher: Plos

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Saks, V. (n.d.). Plos One : the Mitochondrial Na+, Volume 7. Retrieved from http://worldebookfair.com/


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Description : Mitochondria mediate dual metabolic and Ca2+ shuttling activities. While the former is required for Ca2+ signalling linked to insulin secretion, the role of the latter in b cell function has not been well understood, primarily because the molecular identity of the mitochondrial Ca2+ transporters were elusive and the selectivity of their inhibitors was questionable. This study focuses on NCLX, the recently discovered mitochondrial Na+/Ca2+ exchanger that is linked to Ca2+ signalling in MIN6 and primary b cells. Suppression either of NCLX expression, using a siRNA construct (siNCLX) or of its activity, by a dominant negative construct (dnNCLX), enhanced mitochondrial Ca2+ 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 Ca2+. Importantly, NCLX controlled the rate and amplitude of cytosolic Ca2+ 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 Ca2+ signalling. Finally, knockdown of NCLX expression was followed by a delay in glucose-dependent insulin secretion. These findings suggest that the mitochondrial Na+/Ca2+ exchanger, NCLX, shapes glucose-dependent mitochondrial and cytosolic Ca2+ signals thereby regulating the temporal pattern of insulin secretion in b cells.

 

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