线粒体
氧化磷酸化
氧化应激
细胞生物学
Uniporter公司
生物
农奴
线粒体ROS
活性氧
生物化学
ATP酶
胞浆
酶
作者
Enrique Balderas,Sandra Lee,Neeraj Kumar,David M Mollinedo,Hannah E. Duron,Dipayan Chaudhuri
出处
期刊:Physiology
[American Physiological Society]
日期:2024-05-07
标识
DOI:10.1152/physiol.00014.2024
摘要
Oxidative phosphorylation is regulated by mitochondrial calcium (Ca 2+ ) in health and disease. In physiological states, Ca 2+ enters via the mitochondrial Ca 2+ uniporter and rapidly enhances NADH and ATP production. However, maintaining Ca 2+ homeostasis is critical: insufficient Ca 2+ impairs stress adaptation, while Ca 2+ overload can trigger cell death. In this review, we delve into recent insights further defining the relationship between mitochondrial Ca 2+ 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 Ca 2+ regulation is critical for fuel substrate selection, metabolite import, and matching of ATP supply to demand. Second, mitochondrial Ca 2+ 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, Ca 2+ 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 + -Ca 2+ exchanger and may not be noticeable acutely, contributing differently to phenotypes depending on whether Ca 2+ 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 Ca 2+ holds promise as a therapeutic strategy for a variety of cardiac diseases characterized by contractile failure or arrhythmias.
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