Alghamdi Adel
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Al-Baha University, P.O. Box 1988 Al-Baha, Saudi Arabia.
Saudi Pharm J. 2024 Apr;32(4):102012. doi: 10.1016/j.jsps.2024.102012. Epub 2024 Feb 28.
The mitochondria are responsible for the production of cellular ATP, the regulation of cytosolic calcium levels, and the organization of numerous apoptotic proteins through the release of cofactors necessary for the activation of caspases. This level of functional adaptability can only be attained by sophisticated structural alignment. The morphology of the mitochondria does not remain unchanged throughout time; rather, it undergoes change as a result of processes known as fusion and fission. Fzo in flies, Fzo1 in yeast, and mitofusins in mammals are responsible for managing the outer mitochondrial membrane fusion process, whereas Mgm1 in yeast and optic atrophy 1 in mammals are responsible for managing the inner mitochondrial membrane fusion process. The fusion process is composed of two phases. MFN1, a GTPase that is located on the outer membrane of the mitochondria, is involved in the process of linking nearby mitochondria, maintaining the potential of the mitochondrial membrane, and apoptosis. This article offers specific information regarding the functions of MFN1 in a variety of cells and organs found in living creatures. According to the findings of the literature review, MFN1 plays an important part in a number of diseases and organ systems; nevertheless, the protein's function in other disease models and cell types has to be investigated in the near future so that it can be chosen as a promising marker for the therapeutic and diagnostic potentials it possesses. Overall, the major findings of this review highlight the pivotal role of mitofusin (MFN1) in regulating mitochondrial dynamics and its implications across various diseases, including neurodegenerative disorders, cardiovascular diseases, and metabolic syndromes. Our review identifies novel therapeutic targets within the MFN1 signaling pathways and underscores the potential of MFN1 modulation as a promising strategy for treating mitochondrial-related diseases. Additionally, the review calls for further research into MFN1's molecular mechanisms to unlock new avenues for clinical interventions, emphasizing the need for targeted therapies that address MFN1 dysfunction.
线粒体负责细胞ATP的产生、胞质钙水平的调节以及通过释放激活半胱天冬酶所需的辅因子来组织众多凋亡蛋白。这种功能适应性水平只能通过复杂的结构排列来实现。线粒体的形态并非随时间保持不变;相反,它会因融合和裂变等过程而发生变化。果蝇中的Fzo、酵母中的Fzo1以及哺乳动物中的线粒体融合蛋白负责管理线粒体外膜融合过程,而酵母中的Mgm1和哺乳动物中的视神经萎缩蛋白1负责管理线粒体内膜融合过程。融合过程由两个阶段组成。MFN1是一种位于线粒体外膜上的GTP酶,参与连接附近线粒体、维持线粒体膜电位以及凋亡过程。本文提供了有关MFN1在生物体内各种细胞和器官中的功能的具体信息。根据文献综述的结果,MFN1在多种疾病和器官系统中发挥重要作用;然而,该蛋白在其他疾病模型和细胞类型中的功能在不久的将来还有待研究,以便将其作为具有治疗和诊断潜力的有前景的标志物。总体而言,本综述的主要发现突出了线粒体融合蛋白(MFN1)在调节线粒体动力学中的关键作用及其在各种疾病中的意义,包括神经退行性疾病、心血管疾病和代谢综合征。我们的综述确定了MFN1信号通路中的新治疗靶点,并强调调节MFN1作为治疗线粒体相关疾病的有前景策略的潜力。此外,该综述呼吁进一步研究MFN1的分子机制,以开辟新的临床干预途径,强调需要针对MFN1功能障碍的靶向治疗。