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DOI | 10.1016/j.gloenvcha.2016.11.005 |
The mitochondrial Na+/Ca2+ exchanger is essential for Ca2+ homeostasis and viability | |
Luongo, Timothy S.1; Lambert, Jonathan P.1; Gross, Polina2; Nwokedi, Mary1; Lombardi, Alyssa A.1; Shanmughapriya, Santhanam1; Carpenter, April C.3; Kolmetzky, Devin1; Gao, Erhe1; van Berlo, Jop H.4; Tsai, Emily J.5; Molkentin, Jeffery D.6; Chen, Xiongwen2; Madesh, Muniswamy1; Houser, Steven R.2; Elrod, John W.1 | |
2017-05-04 | |
发表期刊 | NATURE
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ISSN | 0028-0836 |
EISSN | 1476-4687 |
出版年 | 2017 |
卷号 | 545期号:7652页码:93-+ |
文章类型 | Article |
语种 | 英语 |
国家 | USA |
英文摘要 | 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. |
领域 | 地球科学 ; 气候变化 ; 资源环境 |
收录类别 | SCI-E |
WOS记录号 | WOS:000400480400037 |
WOS关键词 | CALCIUM UNIPORTER ; ESSENTIAL COMPONENT ; HEART-FAILURE ; MICE LACKING ; PERMEABILITY TRANSITION ; CARDIAC MYOCYTES ; MOUSE ; SURVIVAL ; PROTEIN ; MCU |
WOS类目 | Multidisciplinary Sciences |
WOS研究方向 | Science & Technology - Other Topics |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | http://119.78.100.173/C666/handle/2XK7JSWQ/37845 |
专题 | 气候变化 |
作者单位 | 1.Temple Univ, Sch Med, Ctr Translat Med, Dept Pharmacol, Philadelphia, PA 19140 USA; 2.Temple Univ, Sch Med, Cardiovasc Res Ctr, Dept Physiol, Philadelphia, PA 19140 USA; 3.Ursinus Coll, Dept Hlth & Exercise Physiol, Collegeville, PA 19426 USA; 4.Univ Minnesota, Dept Med, Box 736 UMHC, Minneapolis, MN 55455 USA; 5.Columbia Univ, Coll Phys & Surg, Dept Med, Div Cardiol, New York, NY 10032 USA; 6.Univ Cincinnati, Cincinnati Childrens Hosp Med Ctr, Howard Hughes Med Inst, Dept Pediat, Cincinnati, OH 45229 USA |
推荐引用方式 GB/T 7714 | Luongo, Timothy S.,Lambert, Jonathan P.,Gross, Polina,et al. The mitochondrial Na+/Ca2+ exchanger is essential for Ca2+ homeostasis and viability[J]. NATURE,2017,545(7652):93-+. |
APA | Luongo, Timothy S..,Lambert, Jonathan P..,Gross, Polina.,Nwokedi, Mary.,Lombardi, Alyssa A..,...&Elrod, John W..(2017).The mitochondrial Na+/Ca2+ exchanger is essential for Ca2+ homeostasis and viability.NATURE,545(7652),93-+. |
MLA | Luongo, Timothy S.,et al."The mitochondrial Na+/Ca2+ exchanger is essential for Ca2+ homeostasis and viability".NATURE 545.7652(2017):93-+. |
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