Transient associations between numerous organelles—e.g., the endoplasmic reticulum and the mitochondria—forge highly-coordinated, particular environments essential for cross-compartment information flow. Our perspective summarizes chemical–biology tools that have enabled identifying proteins present within these itinerant communities against the bulk proteome, even when a particular protein's presence is fleeting/substoichiometric. However, proteins resident at these ephemeral junctions also experience transitory changes to their interactomes, small-molecule signalomes, and, importantly, functions. Thus, a thorough census of sub-organellar communities necessitates functionally probing context-dependent signaling properties of individual protein-players. Our perspective accordingly further discusses how repurposing of existing tools could allow us to glean a functional understanding of protein-specific signaling activities altered as a result of organelles pulling together. Collectively, our perspective strives to usher new chemical–biology techniques that could, in turn, open doors to modulate functions of specific subproteomes/organellar junctions underlying the nuanced regulatory subsystem broadly termed as contactology.

中文翻译：

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邻里观察：用于定义依赖于语言环境的亚蛋白质组及其上下文信号活动的工具

众多细胞器之间的瞬时关联——例如、内质网和线粒体——形成高度协调的特殊环境，对跨室信息流至关重要。我们的观点总结了化学生物学工具，这些工具能够针对大量蛋白质组识别这些流动社区中存在的蛋白质，即使特定蛋白质的存在是短暂的/亚化学计量的。然而，驻留在这些短暂连接处的蛋白质也会经历其相互作用组、小分子信号组以及重要的功能的短暂变化。因此，对亚细胞器群落的全面普查需要在功能上探索个体蛋白质参与者的上下文相关信号特性。因此，我们的观点进一步讨论了现有工具的重新利用如何使我们能够收集对由于细胞器聚集在一起而改变的蛋白质特异性信号传导活动的功能理解。总的来说，我们的观点致力于引入新的化学生物学技术，反过来，这些技术可以打开大门来调节特定亚蛋白质组/细胞器连接的功能，这些亚蛋白质组/细胞器连接位于广泛称为接触学的细微调节子系统之下。