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

Jacob E Rysted; Zhihong Lin; Grant C Walters; Adam J Rauckhorst; Maria Noterman; Guanghao Liu; Eric B Taylor; Stefan Strack; Yuriy M Usachev

doi:10.1016/j.ceca.2021.102382

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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

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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

Jacob E Rysted, Zhihong Lin, Grant C Walters, Adam J Rauckhorst, Maria Noterman, Guanghao Liu, Eric B Taylor, Stefan Strack and Yuriy M Usachev

Cell calcium (Edinburgh), Vol.96, pp.102382-102382

06/2021

DOI: 10.1016/j.ceca.2021.102382

PMCID: PMC8187304

PMID: 33684833

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https://www.ncbi.nlm.nih.gov/pmc/articles/8187304View

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Abstract

[Display omitted] •Mitochondrial Na+/Ca2+ exchanger is active in brain and heart, but not in liver.•NCLX is expressed in brain, heart and liver.•Li+ is significantly less effective than Na+ in driving mitochondrial Ca2+ efflux. 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.

Mitochondria

NCX

Hippocampal neurons

NCLX

Ca2+ transport

Details

Title: Subtitle: Distinct properties of Ca2+ efflux from brain, heart and liver mitochondria: The effects of Na+, Li+ and the mitochondrial Na+/Ca2+ exchange inhibitor CGP37157
Creators: Jacob E Rysted - Department of Neuroscience and Pharmacology and Iowa Neuroscience Institute, University of Iowa College of Medicine, Iowa City, IA, 52242, USA
Zhihong Lin - Department of Neuroscience and Pharmacology and Iowa Neuroscience Institute, University of Iowa College of Medicine, Iowa City, IA, 52242, USA
Grant C Walters - Department of Neuroscience and Pharmacology and Iowa Neuroscience Institute, University of Iowa College of Medicine, Iowa City, IA, 52242, USA
Adam J Rauckhorst - Department of Molecular Physiology and Biophysics, University of Iowa College of Medicine, Iowa City, IA, 52242, USA
Maria Noterman - Department of Molecular Physiology and Biophysics, University of Iowa College of Medicine, Iowa City, IA, 52242, USA
Guanghao Liu - Department of Internal Medicine, University of Iowa College of Medicine, Iowa City, IA, 52242, USA
Eric B Taylor - Department of Molecular Physiology and Biophysics, University of Iowa College of Medicine, Iowa City, IA, 52242, USA
Stefan Strack - Department of Neuroscience and Pharmacology and Iowa Neuroscience Institute, University of Iowa College of Medicine, Iowa City, IA, 52242, USA
Yuriy M Usachev - Department of Neuroscience and Pharmacology and Iowa Neuroscience Institute, University of Iowa College of Medicine, Iowa City, IA, 52242, USA
Resource Type: Journal article
Publication Details: Cell calcium (Edinburgh), Vol.96, pp.102382-102382
DOI: 10.1016/j.ceca.2021.102382
PMID: 33684833
PMCID: PMC8187304
NLM abbreviation: Cell Calcium
ISSN: 0143-4160
eISSN: 1532-1991
Publisher: Elsevier Ltd
Grant note: DOI: 10.13039/100000002, name: NIH
Language: English
Date published: 06/2021
Academic Unit: Neurology; Molecular Physiology and Biophysics; Pathology; Iowa Neuroscience Institute; Anesthesia; Fraternal Order of Eagles Diabetes Research Center; Neuroscience and Pharmacology
Record Identifier: 9984070237302771

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