线粒体钙对健康和疾病中心脏代谢的调节。

IF 5.3 2区 医学 Q1 PHYSIOLOGY Physiology Pub Date : 2024-09-01 Epub Date: 2024-05-07 DOI:10.1152/physiol.00014.2024
Enrique Balderas, Sandra H J Lee, Neeraj K Rai, David M Mollinedo, Hannah E Duron, Dipayan Chaudhuri
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引用次数: 0

摘要

在健康和疾病状态下,氧化磷酸化受线粒体钙(Ca2+)的调节。在生理状态下,Ca2+ 通过线粒体 Ca2+ 单通道进入线粒体,并迅速增强 NADH 和 ATP 的生成。然而,维持 Ca2+ 的平衡至关重要:Ca2+ 不足会影响应激适应,而 Ca2+ 过载则会引发细胞死亡。在这篇综述中,我们将深入探讨进一步明确线粒体 Ca2+ 动态与氧化磷酸化之间关系的最新见解。我们的重点是这种调节如何影响健康和疾病中的心脏功能,包括心力衰竭、缺血再灌注、心律失常、儿茶酚胺能多形性室性心动过速、线粒体心肌病、巴特综合征和弗里德里希共济失调。最近的数据提出了几个主题。首先,线粒体 Ca2+ 调节对燃料底物选择、代谢产物输入和 ATP 供需匹配至关重要。其次,线粒体 Ca2+ 调节活性氧(ROS)的产生和反应,其促氧化作用和抗氧化作用之间的平衡是线粒体 Ca2+ 如何促进生理和病理状态的关键。第三,Ca2+ 对电子传递链(ETC)产生局部效应,但不是通过传统的异构机制,而是间接的。这些影响取决于特定的转运体,如单向转运体或 Na+-Ca2+ 交换体,而且在急性期可能并不明显,表型的形成取决于 Ca2+ 转运体是急性改变还是慢性改变。在疾病状态下,这些新型关系的紊乱可能会成为一种补偿机制,也可能会加剧氧化磷酸化的损伤。因此,以线粒体 Ca2+ 为靶点有望成为以收缩功能衰竭或心律失常为特征的多种心脏疾病的治疗策略。
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Mitochondrial Calcium Regulation of Cardiac Metabolism in Health and Disease.

Oxidative phosphorylation is regulated by mitochondrial calcium (Ca2+) in health and disease. In physiological states, Ca2+ enters via the mitochondrial Ca2+ uniporter and rapidly enhances NADH and ATP production. However, maintaining Ca2+ homeostasis is critical: insufficient Ca2+ impairs stress adaptation, and Ca2+ overload can trigger cell death. In this review, we delve into recent insights further defining the relationship between mitochondrial Ca2+ dynamics and oxidative phosphorylation. Our focus is on how such regulation affects cardiac function in health and disease, including heart failure, ischemia-reperfusion, arrhythmias, catecholaminergic polymorphic ventricular tachycardia, mitochondrial cardiomyopathies, Barth syndrome, and Friedreich's ataxia. Several themes emerge from recent data. First, mitochondrial Ca2+ regulation is critical for fuel substrate selection, metabolite import, and matching of ATP supply to demand. Second, mitochondrial Ca2+ regulates both the production and response to reactive oxygen species (ROS), and the balance between its pro- and antioxidant effects is key to how it contributes to physiological and pathological states. Third, Ca2+ exerts localized effects on the electron transport chain (ETC), not through traditional allosteric mechanisms but rather indirectly. These effects hinge on specific transporters, such as the uniporter or the Na+/Ca2+ exchanger, and may not be noticeable acutely, contributing differently to phenotypes depending on whether Ca2+ transporters are acutely or chronically modified. Perturbations in these novel relationships during disease states may either serve as compensatory mechanisms or exacerbate impairments in oxidative phosphorylation. Consequently, targeting mitochondrial Ca2+ holds promise as a therapeutic strategy for a variety of cardiac diseases characterized by contractile failure or arrhythmias.

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来源期刊
Physiology
Physiology 医学-生理学
CiteScore
14.50
自引率
0.00%
发文量
37
期刊介绍: Physiology journal features meticulously crafted review articles penned by esteemed leaders in their respective fields. These articles undergo rigorous peer review and showcase the forefront of cutting-edge advances across various domains of physiology. Our Editorial Board, comprised of distinguished leaders in the broad spectrum of physiology, convenes annually to deliberate and recommend pioneering topics for review articles, as well as select the most suitable scientists to author these articles. Join us in exploring the forefront of physiological research and innovation.
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