Rodriguez Raphaël, Müller Sebastian, Colombeau Ludovic, Solier Stéphanie, Sindikubwabo Fabien, Cañeque Tatiana
Institut Curie, CNRS, INSERM, PSL Research University, 75005 Paris, France.
Université Paris-Saclay, UVSQ, 78180 Montigny-le-Bretonneux, France.
Chem Rev. 2025 Jan 22;125(2):660-744. doi: 10.1021/acs.chemrev.4c00577. Epub 2025 Jan 2.
Complex multicellular organisms are composed of distinct tissues involving specialized cells that can perform specific functions, making such life forms possible. Species are defined by their genomes, and differences between individuals within a given species directly result from variations in their genetic codes. While genetic alterations can give rise to disease-causing acquisitions of distinct cell identities, it is now well-established that biochemical imbalances within a cell can also lead to cellular dysfunction and diseases. Specifically, nongenetic chemical events orchestrate cell metabolism and transcriptional programs that govern functional cell identity. Thus, imbalances in cell signaling, which broadly defines the conversion of extracellular signals into intracellular biochemical changes, can also contribute to the acquisition of diseased cell states. Metal ions exhibit unique chemical properties that can be exploited by the cell. For instance, metal ions maintain the ionic balance within the cell, coordinate amino acid residues or nucleobases altering folding and function of biomolecules, or directly catalyze specific chemical reactions. Thus, metals are essential cell signaling effectors in normal physiology and disease. Deciphering metal ion signaling is a challenging endeavor that can illuminate pathways to be targeted for therapeutic intervention. Here, we review key cellular processes where metal ions play essential roles and describe how targeting metal ion signaling pathways has been instrumental to dissecting the biochemistry of the cell and how this has led to the development of effective therapeutic strategies.
复杂的多细胞生物由不同的组织组成，这些组织包含能够执行特定功能的特化细胞，从而使这些生命形式成为可能。物种由其基因组定义，给定物种内个体之间的差异直接源于其遗传密码的变异。虽然基因改变可导致获得具有不同细胞身份的致病因素，但现在已经明确，细胞内的生化失衡也可导致细胞功能障碍和疾病。具体而言，非遗传化学事件调控着细胞代谢和决定功能性细胞身份的转录程序。因此，细胞信号传导的失衡，广义上定义为细胞外信号转化为细胞内生化变化，也可能导致患病细胞状态的出现。金属离子具有独特的化学性质，可被细胞利用。例如，金属离子维持细胞内的离子平衡，配位氨基酸残基或核碱基，改变生物分子的折叠和功能，或直接催化特定的化学反应。因此，金属在正常生理和疾病中是重要的细胞信号传导效应物。解读金属离子信号传导是一项具有挑战性的工作，它可以阐明可供治疗干预靶向的途径。在这里，我们综述了金属离子发挥重要作用的关键细胞过程，并描述了靶向金属离子信号通路如何有助于剖析细胞生物化学，以及这如何导致了有效治疗策略的发展。
