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Distinct properties of Ca2+ efflux from brain, heart and liver mitochondria: The effects of Na+, Li+ and the mitochondrial Na+/Ca2+ exchange inhibitor CGP37157.


ABSTRACT: Mitochondrial Ca2+ transport is essential for regulating cell bioenergetics, Ca2+ signaling and cell death. Mitochondria accumulate Ca2+ via the mitochondrial Ca2+ uniporter (MCU), whereas Ca2+ is extruded by the mitochondrial Na+/Ca2+ (mtNCX) and H+/Ca2+ exchangers. The balance between these processes is essential for preventing toxic mitochondrial Ca2+ overload. Recent work demonstrated that MCU activity varies significantly among tissues, likely reflecting tissue-specific Ca2+ signaling and energy needs. It is less clear whether this diversity in MCU activity is matched by tissue-specific diversity in mitochondrial Ca2+ extrusion. Here we compared properties of mitochondrial Ca2+ extrusion in three tissues with prominent mitochondria function: brain, heart and liver. At the transcript level, expression of the Na+/Ca2+/Li+ exchanger (NCLX), which has been proposed to mediate mtNCX transport, was significantly greater in liver than in brain or heart. At the functional level, Na+ robustly activated Ca2+ efflux from brain and heart mitochondria, but not from liver mitochondria. The mtNCX inhibitor CGP37157 blocked Ca2+ efflux from brain and heart mitochondria but had no effect in liver mitochondria. Replacement of Na+ with Li+ to test the involvement of NCLX, resulted in a slowing of mitochondrial Ca2+ efflux by ∼70 %. Collectively, our findings suggest that mtNCX is responsible for Ca2+ extrusion from the mitochondria of the brain and heart, but plays only a small, if any, role in mitochondria of the liver. They also reveal that Li+ is significantly less effective than Na+ in driving mitochondrial Ca2+ efflux.

SUBMITTER: Rysted JE 

PROVIDER: S-EPMC8187304 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature

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Distinct properties of Ca<sup>2+</sup> efflux from brain, heart and liver mitochondria: The effects of Na<sup>+</sup>, Li<sup>+</sup> and the mitochondrial Na<sup>+</sup>/Ca<sup>2+</sup> exchange inhibitor CGP37157.

Rysted Jacob E JE   Lin Zhihong Z   Walters Grant C GC   Rauckhorst Adam J AJ   Noterman Maria M   Liu Guanghao G   Taylor Eric B EB   Strack Stefan S   Usachev Yuriy M YM  

Cell calcium 20210222


Mitochondrial Ca<sup>2+</sup> transport is essential for regulating cell bioenergetics, Ca<sup>2+</sup> signaling and cell death. Mitochondria accumulate Ca<sup>2+</sup> via the mitochondrial Ca<sup>2+</sup> uniporter (MCU), whereas Ca<sup>2+</sup> is extruded by the mitochondrial Na<sup>+</sup>/Ca<sup>2+</sup> (mtNCX) and H<sup>+</sup>/Ca<sup>2+</sup> exchangers. The balance between these processes is essential for preventing toxic mitochondrial Ca<sup>2+</sup> overload. Recent work demonstrate  ...[more]

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