Zhang Bingsen, Schroeder Frank C
Boyce Thompson Institute, Cornell University, Ithaca, NY, USA.
Department of Chemistry and Chemical Biology, Cornell University, Ithaca, NY, USA.
Nat Chem Biol. 2025 Jan 7. doi: 10.1038/s41589-024-01805-z.
Intricate coupling between metabolism and protein post-translational modifications (PTMs) has emerged as a fundamental aspect of cellular regulation. Recent studies demonstrate that protein modifications can originate from diverse metabolites, and that their regulation is closely tied to the cellular metabolic state. Here we explore recently uncovered PTMs, including the concept of 'modification of a modification', as well as associated feedback and feedforward regulatory mechanisms, in which modified proteins impact not only related metabolic pathways but also other signaling cascades affecting physiology and diseases. The recently uncovered role of nucleus-localized metabolic enzymes for histone modifications additionally highlights the importance of cell-compartment-specific metabolic states. We further comment on the utility of untargeted metabolomics and proteomics for previously unrecognized PTMs and associated metabolic patterns. Together, these advances have uncovered a dynamic interplay between metabolism and PTMs, offering new perspectives for understanding metabolic regulation and developing targeted therapeutic strategies.
代谢与蛋白质翻译后修饰（PTM）之间复杂的耦合作用已成为细胞调控的一个基本方面。最近的研究表明，蛋白质修饰可源自多种代谢物，且其调控与细胞代谢状态密切相关。在此，我们探讨最近发现的PTM，包括“修饰的修饰”概念，以及相关的反馈和前馈调节机制，其中修饰的蛋白质不仅影响相关代谢途径，还影响其他影响生理和疾病的信号级联反应。最近发现的细胞核定位代谢酶对组蛋白修饰的作用进一步凸显了细胞区室特异性代谢状态的重要性。我们还评论了非靶向代谢组学和蛋白质组学在识别以前未被认识的PTM和相关代谢模式方面的效用。总之，这些进展揭示了代谢与PTM之间的动态相互作用，为理解代谢调控和制定靶向治疗策略提供了新的视角。
