Matrix revisited: mechanisms linking energy substrate metabolism to the function of the heart.
Matrix revisited: mechanisms linking energy substrate metabolism to the function of the heart.
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DOI：
10.1161/circresaha.114.301863
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发表时间：
2014-02-14
影响因子：
20.1
通讯作者：
Lewandowski ED
中科院分区：
文献类型：
--
作者：
Carley AN;Taegtmeyer H;Lewandowski ED
代谢信号传导机制越来越多地被认为是介导细胞对工作负荷需求变化的反应，这是生理和病理生理挑战的结果。因此，了解细胞质中的代谢机制与线粒体基质中的能量提供途径协调活动对于加深我们对应激心肌细胞中发生的致病变化的了解至关重要。在细胞质和线粒体之间交换代谢中间产物和阳离子的过程使得能够将收缩状态的动态变化转导到细胞的线粒体区室。这种代谢转导途径的破坏对心脏收缩功能的有力支持具有严重后果，并且与心力衰竭的发病机制有关。心肌细胞中代谢储备的缺陷和代谢转导的受损可能是由于代谢表型的固有缺陷或代谢酶表达和调节对病原性应激的反应中的适应不良变化。这篇评论探讨了当前和新兴的概念之间的功能联系的细胞质和线粒体基质的代谢储备和能量效率的具体重点。本文从慢性压力超负荷和糖尿病的角度综述了线粒体跨膜交换和转运机制在心力衰竭中的作用。
Metabolic signaling mechanisms are increasingly recognized to mediate the cellular response to alterations in workload demand, as a consequence of physiological and pathophysiological challenges. Thus, an understanding of the metabolic mechanisms coordinating activity in the cytosol with the energy-providing pathways in the mitochondrial matrix becomes critical for deepening our insights into the pathogenic changes that occur in the stressed cardiomyocyte. Processes that exchange both metabolic intermediates and cations between the cytosol and mitochondria enable transduction of dynamic changes in contractile state to the mitochondrial compartment of the cell. Disruption of such metabolic transduction pathways has severe consequences for the energetic support of contractile function in the heart and is implicated in the pathogenesis of heart failure. Deficiencies in metabolic reserve and impaired metabolic transduction in the cardiomyocyte can result from inherent deficiencies in metabolic phenotype or maladaptive changes in metabolic enzyme expression and regulation in the response to pathogenic stress. This review examines both current and emerging concepts of the functional linkage between the cytosol and the mitochondrial matrix with a specific focus on metabolic reserve and energetic efficiency. These principles of exchange and transport mechanisms across the mitochondrial membrane are reviewed for the failing heart from the perspectives of chronic pressure overload and diabetes mellitus.