The mitochondrial Na+/Ca2+ exchanger is essential for Ca2+ homeostasis and viability

Luongo Timothy S.; Lambert Jonathan P.; Gross Polina; Nwokedi Mary; Lombardi Alyssa A.; Shanmughapriya Santhanam; Carpenter April C.; Kolmetzky Devin; Gao Erhe; van Berlo Jop H.; Tsai Emily J.; Molkentin Jeffery D.; Chen Xiongwen; Madesh Muniswamy; Houser Steven R.; Elrod John W.

首页> 外文期刊>Nature >The mitochondrial Na+/Ca2+ exchanger is essential for Ca2+ homeostasis and viability

【24h】

The mitochondrial Na+/Ca2+ exchanger is essential for Ca2+ homeostasis and viability

机译：线粒体Na + / Ca2 +交换子对于Ca2 +稳态和生存力至关重要

获取原文

获取原文并翻译 | 示例

掌桥外文数据库（机构版） >>

开具论文收录证明 >>

文献代查 >>

页面导航

摘要
著录项
相似文献
相关主题

摘要

Mitochondrial calcium (Ca-m(2+)) has a central role in both metabolic regulation and cell death signalling, however its role in homeostatic function and disease is controversial(1). Slc8b1 encodes the mitochondrial Na+/Ca2+ exchanger (NCLX), which is proposed to be the primary mechanism for mCa2+ extrusion in excitable cells(2,3). Here we show that tamoxifen-induced deletion of Slc8b1 in adult mouse hearts causes sudden death, with less than 13% of affected mice surviving after 14 days. Lethality correlated with severe myocardial dysfunction and fulminant heart failure. Mechanistically, cardiac pathology was attributed to mCa(2+) overload driving increased generation of superoxide and necrotic cell death, which was rescued by genetic inhibition of mitochondrial permeability transition pore activation. Corroborating these findings, overexpression of NCLX in the mouse heart by conditional transgenesis had the beneficial effect of augmenting mCa(2+) clearance, preventing permeability transition and protecting against ischaemia-induced cardiomyocyte necrosis and heart failure. These results demonstrate the essential nature of mCa(2+) efflux in cellular function and suggest that augmenting mCa(2+) efflux may be a viable therapeutic strategy in disease.

机译：线粒体钙（Ca-m（2+））在代谢调节和细胞死亡信号传导中都起着核心作用，但是其在体内稳态功能和疾病中的作用尚有争议（1）。 Slc8b1编码线粒体Na + / Ca2 +交换子（NCLX），被认为是可兴奋细胞中mCa2 +挤出的主要机制（2,3）。在这里，我们显示他莫昔芬诱导的成年小鼠心脏中Slc8b1的缺失导致猝死，不到13％的受影响小鼠在14天后存活。致命性与严重的心肌功能障碍和暴发性心力衰竭相关。从机理上讲，心脏病理学归因于mCa（2+）超载驱动增加的超氧化物和坏死细胞死亡的产生，这是通过线粒体通透性过渡孔激活的基因抑制来挽救的。证实这些发现，通过条件转基因在小鼠心脏中NCLX的过表达具有增加mCa（2+）清除率，防止渗透性转变并防止缺血引起的心肌细胞坏死和心力衰竭的有益作用。这些结果表明细胞功能中的mCa（2+）外排的本质，并建议增加mCa（2+）外排可能是疾病中可行的治疗策略。

著录项

来源
《Nature》 |2017年第7652期|93-97|共5页
作者
Luongo Timothy S.; Lambert Jonathan P.; Gross Polina; Nwokedi Mary; Lombardi Alyssa A.; Shanmughapriya Santhanam; Carpenter April C.; Kolmetzky Devin; Gao Erhe; van Berlo Jop H.; Tsai Emily J.; Molkentin Jeffery D.; Chen Xiongwen; Madesh Muniswamy; Houser Steven R.; Elrod John W.;
展开▼
作者单位

Temple Univ, Sch Med, Ctr Translat Med, Dept Pharmacol, Philadelphia, PA 19140 USA;

Temple Univ, Sch Med, Ctr Translat Med, Dept Pharmacol, Philadelphia, PA 19140 USA;

Temple Univ, Sch Med, Cardiovasc Res Ctr, Dept Physiol, Philadelphia, PA 19140 USA;

Temple Univ, Sch Med, Ctr Translat Med, Dept Pharmacol, Philadelphia, PA 19140 USA;

Temple Univ, Sch Med, Ctr Translat Med, Dept Pharmacol, Philadelphia, PA 19140 USA;

Temple Univ, Sch Med, Ctr Translat Med, Dept Pharmacol, Philadelphia, PA 19140 USA;

Ursinus Coll, Dept Hlth & Exercise Physiol, Collegeville, PA 19426 USA;

Temple Univ, Sch Med, Ctr Translat Med, Dept Pharmacol, Philadelphia, PA 19140 USA;

Temple Univ, Sch Med, Ctr Translat Med, Dept Pharmacol, Philadelphia, PA 19140 USA;

Univ Minnesota, Dept Med, Box 736 UMHC, Minneapolis, MN 55455 USA;

Columbia Univ, Coll Phys & Surg, Dept Med, Div Cardiol, New York, NY 10032 USA;

Univ Cincinnati, Cincinnati Childrens Hosp Med Ctr, Howard Hughes Med Inst, Dept Pediat, Cincinnati, OH 45229 USA;

Temple Univ, Sch Med, Cardiovasc Res Ctr, Dept Physiol, Philadelphia, PA 19140 USA;

Temple Univ, Sch Med, Ctr Translat Med, Dept Pharmacol, Philadelphia, PA 19140 USA;

Temple Univ, Sch Med, Cardiovasc Res Ctr, Dept Physiol, Philadelphia, PA 19140 USA;

Temple Univ, Sch Med, Ctr Translat Med, Dept Pharmacol, Philadelphia, PA 19140 USA;

展开▼
收录信息美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
原文格式 PDF
正文语种 eng
中图分类
关键词

相似文献

外文文献
中文文献
专利

1. The Mitochondrial Na+/Ca2+ Exchanger is Necessary but Not Sufficient for Ca2+ Homeostasis and Viability [J] . Liu Timon Cheng-Yi, Tang Xiao-Ming, Duan Rui, Advances in Experimental Medicine and Biology . 2018,第期

机译：线粒体Na + / Ca2 +交换器是必需的，但不足以足以满足Ca2 +稳态和可行性
2. Mitochondrial Ca2+ Processing by a Unit of Mitochondrial Ca2+ Uniporter and Na+/Ca2+ Exchanger Supports the Neuronal Ca2+ Influx via Activated Glutamate Receptors [J] . Strokin Mikhail, Reiser Georg Neurochemical research . 2016,第6期

机译：线粒体Ca2 +单向转运蛋白和Na + / Ca2 +交换子对线粒体Ca2 +的加工通过活化的谷氨酸受体支持神经元Ca2 +流入。
3. Sequestration of depolarization-induced Ca2+ loads by mitochondria and Ca2+ efflux via mitochondrial Na+/Ca2+ exchanger in bovine adrenal chromaffin cells. [J] . Sorimachi M, Nishimura S, Yamagami K The Japanese journal of physiology . 1999,第1期

机译：线粒体的去极化诱导的Ca2 +负载和通过线粒体Na + / Ca2 +交换子的Ca2 +外排隔离在牛肾上腺嗜铬细胞中。
4. An Engineering-Optimized Cardiac Pacemaker by Manipulating Na+/Ca2+ Exchange Current and Na+/K+ Pumping Current [C] . Yacong Li, Kuanquan Wang, Qince Li, Computing in Cardiology Conference . 2019

机译：通过操纵Na + / ca 2 + 交换电流和Na + / k + 泵送电流
5. Functional Characterization of Na+/Ca2+ Exchangers in Caenorhabditis elegans. [D] . Sharma, Vishal. 2017

机译：秀丽隐杆线虫中Na + / Ca2 +交换子的功能表征。
6. The mitochondrial Na+/Ca2+exchanger is essential for Ca2+ homeostasis andviability [O] . Timothy S. Luongo, Jonathan P. Lambert, Polina Gross, -1

机译：线粒体Na + / Ca2 +交换器对于Ca2 +稳态和可行性
7. Glycine release provoked by disturbed Na+, K+ and Ca2+ homeostasis in cerebellar nerve endings: roles of Ca2+ channels, Na+/Ca2+ exchangers and GlyT2 transporter reversal [O] . Romei C, Di Prisco S, Raiteri M, 2011

机译：小脑神经末梢紊乱的Na +，K +和Ca2 +稳态引起的甘氨酸释放：Ca2 +通道，Na + / Ca2 +交换子和GlyT2转运蛋白逆转的作用

The mitochondrial Na+/Ca2+ exchanger is essential for Ca2+ homeostasis and viability

摘要

著录项

相似文献

相关主题

期刊订阅