Department of Bioinformatics, The Islamia University of Bahawalpur, Bahawalpur, Punjab, Pakistan.
Department of Bioinformatics, University of Okara, Okara, Pakistan.
Curr Neuropharmacol. 2023;21(5):1026-1041. doi: 10.2174/1570159X21666230314140528.
With the advancement in novel drug discovery, biologically active compounds are considered pharmacological tools to understand complex biological mechanisms and the identification of potent therapeutic agents. Mitochondria boast a central role in different integral biological processes and mitochondrial dysfunction is associated with multiple pathologies. It is, therefore, prudent to target mitochondrial quality control mechanisms by using pharmacological approaches. However, there is a scarcity of biologically active molecules, which can interact with mitochondria directly. Currently, the chemical compounds used to induce mitophagy include oligomycin and antimycin A for impaired respiration and acute dissipation of mitochondrial membrane potential by using CCCP/FCCP, the mitochondrial uncouplers. These chemical probes alter the homeostasis of the mitochondria and limit our understanding of the energy regulatory mechanisms. Efforts are underway to find molecules that can bring about selective removal of defective mitochondria without compromising normal mitochondrial respiration. In this report, we have tried to summarize and status of the recently reported modulators of mitophagy.
随着新型药物发现的进展,生物活性化合物被认为是药理学工具,可用于了解复杂的生物学机制和鉴定有效的治疗剂。线粒体在不同的整体生物过程中发挥着核心作用,线粒体功能障碍与多种病理有关。因此,通过使用药理学方法靶向线粒体质量控制机制是谨慎的。然而,目前能够直接与线粒体相互作用的生物活性分子却很少。目前,用于诱导自噬的化学化合物包括寡霉素和抗霉素 A,用于因 CCCP/FCCP(线粒体解偶联剂)而受损的呼吸和线粒体膜电位的急性耗散。这些化学探针改变了线粒体的内稳态,限制了我们对能量调节机制的理解。目前正在努力寻找可以选择性去除有缺陷的线粒体而不影响正常线粒体呼吸的分子。在本报告中,我们试图总结和评估最近报道的自噬调节剂的状态。