Complex I deficiency due to selective loss of Ndufs4 in the mouse heart results in severe hypertrophic cardiomyopathy.
Complex I deficiency due to selective loss of Ndufs4 in the mouse heart results in severe hypertrophic cardiomyopathy.
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DOI：
10.1371/journal.pone.0094157
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Krieg T
中科院分区：
文献类型：
--
作者：
Chouchani ET;Methner C;Buonincontri G;Hu CH;Logan A;Sawiak SJ;Murphy MP;Krieg T
线粒体复合体 I 是电子进入线粒体呼吸链的主要入口点，对于有氧呼吸至关重要，也是活性氧的主要来源。在心脏中，导致心肌病的慢性功能障碍通常与遗传和环境原因导致的复合物 I 活性降低有关。为了检查复合物 I 破坏和心脏功能障碍之间的功能关系，我们使用了通过心脏特异性 Ndufs4 基因消融建立的轻度和慢性复合物 I 抑制的小鼠模型。心脏特异性 Ndufs4 缺失小鼠心脏内复合物 I 活性下降约 50%，并通过磁共振成像评估发展为严重肥厚性心肌病。复合物 I 活性的降低和相关的心脏功能障碍是在体内线粒体过氧化氢水平不增加、氧化损伤标志物积累、细胞凋亡诱导或组织纤维化的情况下发生的。总而言之，这些结果表明，仅心脏中复合物 I 活性的降低就足以导致肥厚性心肌病，而与线粒体过氧化氢水平的变化或氧化损伤无关。
Mitochondrial complex I, the primary entry point for electrons into the mitochondrial respiratory chain, is both critical for aerobic respiration and a major source of reactive oxygen species. In the heart, chronic dysfunction driving cardiomyopathy is frequently associated with decreased complex I activity, from both genetic and environmental causes. To examine the functional relationship between complex I disruption and cardiac dysfunction we used an established mouse model of mild and chronic complex I inhibition through heart-specific Ndufs4 gene ablation. Heart-specific Ndufs4-null mice had a decrease of ∼50% in complex I activity within the heart, and developed severe hypertrophic cardiomyopathy as assessed by magnetic resonance imaging. The decrease in complex I activity, and associated cardiac dysfunction, occurred absent an increase in mitochondrial hydrogen peroxide levels in vivo, accumulation of markers of oxidative damage, induction of apoptosis, or tissue fibrosis. Taken together, these results indicate that diminished complex I activity in the heart alone is sufficient to drive hypertrophic cardiomyopathy independently of alterations in levels of mitochondrial hydrogen peroxide or oxidative damage.
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DOI：
10.1042/bj20081386
发表时间：
2009-01-01
期刊：
The Biochemical journal
影响因子：
--
作者：
Murphy MP
通讯作者：
Murphy MP
影响因子：
29
作者：
Cochemé HM;Quin C;McQuaker SJ;Cabreiro F;Logan A;Prime TA;Abakumova I;Patel JV;Fearnley IM;James AM;Porteous CM;Smith RA;Saeed S;Carré JE;Singer M;Gems D;Hartley RC;Partridge L;Murphy MP
通讯作者：
Murphy MP
影响因子：
3.9
作者：
Bridges, Hannah R.;Birrell, James A.;Hirst, Judy
通讯作者：
Hirst, Judy
DOI：
10.1186/1532-429x-14-17
发表时间：
2012-02-20
期刊：
Journal of cardiovascular magnetic resonance : official journal of the Society for Cardiovascular Magnetic Resonance
影响因子：
--
作者：
Noureldin RA;Liu S;Nacif MS;Judge DP;Halushka MK;Abraham TP;Ho C;Bluemke DA
通讯作者：
Bluemke DA
DOI：
10.1073/pnas.1113987109
发表时间：
2012-04-17
影响因子：
11.1
作者：
Ke, Bi-Xia;Pepe, Salvatore;Thorburn, David R.
通讯作者：
Thorburn, David R.