Metals are essential components in life processes and participate in many important biological processes. Dysregulation of metal homeostasis is correlated with many diseases. Metals are also frequently incorporated into diagnosis and therapeutics. Understanding of metal homeostasis under (patho)physiological conditions and the molecular mechanisms of action of metallodrugs in biological systems has positive impacts on human health. As an emerging interdisciplinary area of research, metalloproteomics involves investigating metal-protein interactions in biological systems at a proteome-wide scale, has received growing attention, and has been implemented into metal-related research. In this review, we summarize the recent advances in metalloproteomics methodologies and applications. We also highlight emerging single-cell metalloproteomics, including time-resolved inductively coupled plasma mass spectrometry, mass cytometry, and secondary ion mass spectrometry. Finally, we discuss future perspectives in metalloproteomics, aiming to attract more original research to develop more advanced methodologies, which could be utilized rapidly by biochemists or biologists to expand our knowledge of how metal functions in biology and medicine.

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生物医学研究的金属蛋白质组学：方法和应用

金属是生命过程中的重要组成部分，参与许多重要的生物过程。金属稳态失调与许多疾病相关。金属也经常被纳入诊断和治疗中。了解（病理）生理条件下的金属稳态以及生物系统中金属药物作用的分子机制对人类健康具有积极影响。作为一个新兴的跨学科研究领域，金属蛋白质组学涉及在蛋白质组范围内研究生物系统中金属-蛋白质相互作用，受到越来越多的关注，并已应用于金属相关研究。在这篇综述中，我们总结了金属蛋白质组学方法和应用的最新进展。我们还重点介绍新兴的单细胞金属蛋白质组学，包括时间分辨电感耦合等离子体质谱、质谱流式分析和二次离子质谱。最后，我们讨论了金属蛋白质组学的未来前景，旨在吸引更多的原创研究来开发更先进的方法，生物化学家或生物学家可以快速利用这些方法来扩展我们对金属在生物学和医学中如何发挥作用的知识。