Assessment of cardiac function in mice lacking the mitochondrial calcium uniporter.
Assessment of cardiac function in mice lacking the mitochondrial calcium uniporter.
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DOI：
10.1016/j.yjmcc.2015.05.022
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发表时间：
2015-08
影响因子：
5
通讯作者：
Finkel T
中科院分区：
文献类型：
--
作者：
Holmström KM;Pan X;Liu JC;Menazza S;Liu J;Nguyen TT;Pan H;Parks RJ;Anderson S;Noguchi A;Springer D;Murphy E;Finkel T
线粒体钙被认为在心脏生物能量学和功能的调节中起重要作用。钙进入线粒体基质需要二价阳离子通过一个称为线粒体钙单转运体（MCU）的特殊孔穿过线粒体内膜。在这里，我们使用MCU表达不足的小鼠来严格评估线粒体钙在心功能中的作用。从MCU-/-小鼠中分离的线粒体具有基质钙水平降低、钙摄取受损和钙刺激呼吸缺陷。尽管如此，我们发现MCU表达缺失并不影响12或20月龄时的基础心功能。此外，MCU-/-小鼠对异丙肾上腺素刺激或主动脉横缩的生理反应与对照组小鼠相似。因此，尽管来自MCU-/-小鼠的线粒体明显损害了线粒体钙处理，但这些动物的心脏在基础条件下和压力下出奇地表现出相对正常的功能。
Mitochondrial calcium is thought to play an important role in the regulation of cardiac bioenergetics and function. The entry of calcium into the mitochondrial matrix requires that the divalent cation pass through the inner mitochondrial membrane via a specialized pore known as the mitochondrial calcium uniporter (MCU). Here, we use mice deficient for MCU expression to rigorously assess the role of mitochondrial calcium in cardiac function. Mitochondria isolated from MCU-/- mice have reduced matrix calcium levels, impaired calcium uptake and a defect in calcium-stimulated respiration. Nonetheless, we find that the absence of MCU expression does not affect basal cardiac function at either 12 or 20 months of age. Moreover, the physiological response of MCU-/- mice to isoproterenol challenge or transverse aortic constriction appears similar to control mice. Thus, while mitochondria derived from MCU-/- mice have markedly impaired mitochondrial calcium handling, the hearts of these animals surprisingly appear to function relatively normally under basal conditions and during stress.