背景:在全球范围内,多种人类疾病的发生和进展与线粒体功能障碍和线粒体钙单蛋白(MCU)复合物介导的Ca2摄取动力学失调有关,在线粒体功能障碍中起关键作用。尽管有相关研究,潜在的病理生理机制尚未完全阐明。
目的:本文深入分析了单片机复合体的研究现状,专注于它的分子组成,监管机制,以及与疾病的联系。此外,我们对激动剂的调节作用进行了深入分析,抑制剂,和中药单体在单片机上的复合及其在疾病治疗中的应用前景。从药物化学的角度来看,我们对这些小分子与MCU之间的构效关系进行了深入分析,并推导出潜在的药效团和结合袋.同时,确定了智人MCU复合物的关键结构域。我们还研究了单片机复合物在果蝇中的功能表达,斑马鱼,和秀丽隐杆线虫.这些分析为探索针对MCU复合物的潜在治疗策略提供了基础,并为未来精准医学和治疗的发展提供了强有力的支持。
■MCU复合物在不同组织中表现出不同的行为,并在代谢功能中发挥各种作用。它由六个MCU子单元组成,一个基本的MCU调节器(EMRE),和溶质载体25A23(SLC25A23)。他们规范流程,如线粒体Ca2+(mCa2+)摄取,线粒体三磷酸腺苷(ATP)的生产,钙动力学,氧化应激(OS),细胞死亡。监管使其成为治疗疾病的潜在目标,尤其是心血管疾病,神经退行性疾病,炎症性疾病,代谢性疾病,和肿瘤。
BACKGROUND: Globally, the onset and progression of multiple human diseases are associated with mitochondrial dysfunction and dysregulation of Ca2+ uptake dynamics mediated by the mitochondrial calcium uniporter (MCU) complex, which plays a key role in mitochondrial dysfunction. Despite relevant studies, the underlying pathophysiological mechanisms have not yet been fully elucidated.
OBJECTIVE: This article provides an in-depth analysis of the current research status of the MCU complex, focusing on its molecular composition, regulatory mechanisms, and association with diseases. In addition, we conducted an in-depth analysis of the regulatory effects of agonists, inhibitors, and traditional Chinese medicine (TCM) monomers on the MCU complex and their application prospects in disease treatment. From the perspective of medicinal chemistry, we conducted an in-depth analysis of the structure-activity relationship between these small molecules and MCU and deduced potential pharmacophores and binding pockets. Simultaneously, key structural domains of the MCU complex in Homo sapiens were identified. We also studied the functional expression of the MCU complex in Drosophila, Zebrafish, and Caenorhabditis elegans. These analyses provide a basis for exploring potential treatment strategies targeting the MCU complex and provide strong support for the development of future precision medicine and treatments.
UNASSIGNED: The MCU complex exhibits varying behavior across different tissues and plays various roles in metabolic functions. It consists of six MCU subunits, an essential MCU regulator (EMRE), and solute carrier 25A23 (SLC25A23). They regulate processes, such as mitochondrial Ca2+ (mCa2+) uptake, mitochondrial adenosine triphosphate (ATP) production, calcium dynamics, oxidative stress (OS), and cell death. Regulation makes it a potential target for treating diseases, especially cardiovascular diseases, neurodegenerative diseases, inflammatory diseases, metabolic diseases, and tumors.