Walters Grant C, Usachev Yuriy M
Department of Neuroscience and Pharmacology, Iowa Neuroscience Institute, University of Iowa, Iowa City, IA, United States.
Front Cell Dev Biol. 2023 Jan 24;11:1094356. doi: 10.3389/fcell.2023.1094356. eCollection 2023.
Mitochondria are essential for proper cellular function through their critical roles in ATP synthesis, reactive oxygen species production, calcium (Ca) buffering, and apoptotic signaling. In neurons, Ca buffering is particularly important as it helps to shape Ca signals and to regulate numerous Ca-dependent functions including neuronal excitability, synaptic transmission, gene expression, and neuronal toxicity. Over the past decade, identification of the mitochondrial Ca uniporter (MCU) and other molecular components of mitochondrial Ca transport has provided insight into the roles that mitochondrial Ca regulation plays in neuronal function in health and disease. In this review, we discuss the many roles of mitochondrial Ca uptake and release mechanisms in normal neuronal function and highlight new insights into the Ca-dependent mechanisms that drive mitochondrial dysfunction in neurologic diseases including epilepsy, Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. We also consider how targeting Ca uptake and release mechanisms could facilitate the development of novel therapeutic strategies for neurological diseases.
线粒体对于细胞的正常功能至关重要，因为它们在三磷酸腺苷（ATP）合成、活性氧生成、钙（Ca）缓冲和凋亡信号传导中发挥着关键作用。在神经元中，钙缓冲尤为重要，因为它有助于塑造钙信号，并调节众多依赖钙的功能，包括神经元兴奋性、突触传递、基因表达和神经毒性。在过去十年中，线粒体钙单向转运体（MCU）和线粒体钙转运的其他分子成分的鉴定，为线粒体钙调节在健康和疾病状态下神经元功能中所起的作用提供了深入了解。在这篇综述中，我们讨论了线粒体钙摄取和释放机制在正常神经元功能中的多种作用，并强调了对驱动包括癫痫、阿尔茨海默病、帕金森病和肌萎缩侧索硬化症在内的神经疾病中线粒体功能障碍的钙依赖机制的新见解。我们还考虑了靶向钙摄取和释放机制如何促进神经疾病新治疗策略的开发。
