Boengler Kerstin, Eickelmann Chantal, Kleinbongard Petra
Institute of Physiology, Justus-Liebig University, 35392 Giessen, Germany.
Institute for Pathophysiology, West German Heart and Vascular Center, University of Essen Medical School, 45147 Essen, Germany.
Int J Mol Sci. 2024 Apr 19;25(8):4491. doi: 10.3390/ijms25084491.
Myocardial ischemia/reperfusion injury is reduced by cardioprotective adaptations such as local or remote ischemic conditioning. The cardioprotective stimuli activate signaling cascades, which converge on mitochondria and maintain the function of the organelles, which is critical for cell survival. The signaling cascades include not only extracellular molecules that activate sarcolemmal receptor-dependent or -independent protein kinases that signal at the plasma membrane or in the cytosol, but also involve kinases, which are located to or within mitochondria, phosphorylate mitochondrial target proteins, and thereby modify, e.g., respiration, the generation of reactive oxygen species, calcium handling, mitochondrial dynamics, mitophagy, or apoptosis. In the present review, we give a personal and opinionated overview of selected protein kinases, localized to/within myocardial mitochondria, and summarize the available data on their role in myocardial ischemia/reperfusion injury and protection from it. We highlight the regulation of mitochondrial function by these mitochondrial protein kinases.
心肌缺血/再灌注损伤可通过心脏保护适应性机制（如局部或远程缺血预处理）得以减轻。心脏保护刺激激活信号级联反应，这些反应汇聚于线粒体并维持细胞器的功能，而这对细胞存活至关重要。信号级联反应不仅包括激活肌膜受体依赖性或非依赖性蛋白激酶的细胞外分子，这些蛋白激酶在质膜或胞质溶胶中发挥信号作用，还涉及定位于线粒体或线粒体内的激酶，它们使线粒体靶蛋白磷酸化，从而改变（例如）呼吸作用、活性氧的产生、钙处理、线粒体动力学、线粒体自噬或细胞凋亡。在本综述中，我们对定位于心肌线粒体或线粒体内的特定蛋白激酶进行了个人化且带有观点性的概述，并总结了关于它们在心肌缺血/再灌注损伤及其保护作用中所起作用的现有数据。我们强调了这些线粒体蛋白激酶对线粒体功能的调节作用。
