Huang Kuan-Ting, Aye Yimon
Swiss Federal Institute of Technology Lausanne (EPFL), Lausanne, Switzerland.
University of Oxford, Oxford, UK.
Commun Chem. 2024 Sep 2;7(1):195. doi: 10.1038/s42004-024-01282-4.
Immune-cell reprogramming driven by mitochondria-derived reactive electrophilic immunometabolites (mt-REMs-e.g., fumarate, itaconate) is an emerging phenomenon of major biomedical importance. Despite their localized production, mt-REMs elicit significantly large local and global footprints within and across cells, through mechanisms involving electrophile signaling. Burgeoning efforts are being put into profiling mt-REMs' potential protein-targets and phenotypic mapping of their multifaceted inflammatory behaviors. Yet, precision indexing of mt-REMs' first-responders with spatiotemporal intelligence and locale-specific function assignments remain elusive. Highlighting the latest advances and overarching challenges, this perspective aims to stimulate thoughts and spur interdisciplinary innovations to address these unmet chemical-biotechnological needs at therapeutic immuno-signaling frontiers.
由线粒体衍生的反应性亲电免疫代谢物（mt-REMs，如富马酸、衣康酸）驱动的免疫细胞重编程是一种具有重大生物医学意义的新现象。尽管mt-REMs是局部产生的，但它们通过涉及亲电信号传导的机制，在细胞内和细胞间引发了显著的局部和全局影响。目前正在蓬勃开展工作，以分析mt-REMs的潜在蛋白质靶点，并对其多方面炎症行为进行表型映射。然而，对mt-REMs的第一反应者进行具有时空智能和局部特异性功能分配的精确索引仍然难以实现。本观点突出了最新进展和总体挑战，旨在激发思考并推动跨学科创新，以满足治疗性免疫信号前沿这些未得到满足的化学生物技术需求。
