Salazar-Ramírez Felipe, Ramos-Mondragón Roberto, García-Rivas Gerardo
Tecnologico de Monterrey, Escuela de Medicina y Ciencias de la Salud, Cátedra de Cardiología y Medicina Cardiovascular, Monterrey, Mexico.
Department of Pharmacology, University of Michigan Medical School, Ann Arbor, MI, United States.
Front Cell Dev Biol. 2021 Jan 28;8:623381. doi: 10.3389/fcell.2020.623381. eCollection 2020.
Ca plays a pivotal role in mitochondrial energy production, contraction, and apoptosis. Mitochondrial Ca-targeted fluorescent probes have demonstrated that mitochondria Ca transients are synchronized with Ca fluxes occurring in the sarcoplasmic reticulum (SR). The presence of specialized proteins tethering SR to mitochondria ensures the local Ca flux between these organelles. Furthermore, communication between SR and mitochondria impacts their functionality in a bidirectional manner. Mitochondrial Ca uptake through the mitochondrial Ca uniplex is essential for ATP production and controlled reactive oxygen species levels for proper cellular signaling. Conversely, mitochondrial ATP ensures the proper functioning of SR Ca-handling proteins, which ensures that mitochondria receive an adequate supply of Ca. Recent evidence suggests that altered SR Ca proteins, such as ryanodine receptors and the sarco/endoplasmic reticulum Ca ATPase pump, play an important role in maintaining proper cardiac membrane excitability, which may be initiated and potentiated when mitochondria are dysfunctional. This recognized mitochondrial role offers the opportunity to develop new therapeutic approaches aimed at preventing cardiac arrhythmias in cardiac disease.
钙在线粒体能量产生、收缩和凋亡过程中发挥着关键作用。线粒体钙靶向荧光探针已证明，线粒体钙瞬变与肌浆网（SR）中发生的钙通量同步。将SR与线粒体相连的特殊蛋白质的存在确保了这些细胞器之间的局部钙通量。此外，SR与线粒体之间的通讯以双向方式影响它们的功能。通过线粒体钙单向转运体摄取线粒体钙对于ATP生成以及维持适当的细胞信号传导所需的活性氧水平至关重要。相反，线粒体ATP确保了SR钙处理蛋白的正常功能，从而确保线粒体获得充足的钙供应。最近的证据表明，诸如兰尼碱受体和肌浆网/内质网钙ATP酶泵等SR钙蛋白的改变在维持适当的心脏膜兴奋性方面发挥着重要作用，当线粒体功能失调时，这种兴奋性可能会被引发和增强。这种已被认可的线粒体作用为开发旨在预防心脏病中心律失常的新治疗方法提供了机会。
