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Article Abstract
D-2-Hydroxyglutarate (D-2-HG) is a functional endogenous metabolite in various domains of life. Its abnormal accumulation promotes human tumorigenesis. Convenient D-2-HG testing for diagnosis and prognosis of D-2-HG-related diseases remains technically challenging, and there is no analytical method to directly detect D-2-HG in living cells. Here, we identify a D-2-HG-specific transcriptional activator, HgcR, and develop a d-2-HG sensor (DHOR) using HgcR as a sensing moiety. Then, we build a portable device adaptive with DHOR for rapid and low-cost point-of-care D-2-HG testing in serum, urine, and glioma tissue samples. DHOR also allow spatiotemporal resolution of D-2-HG in living bacteria and human cells. We use DHOR to identify D-2-HG transporters from Escherichia coli and human solute carrier 22 family. Overall, DHOR provides a powerful and versatile tool for in vitro and live-cell detection of D-2-HG, offering the opportunity to deepen our understanding about physiological and pathogenetic roles of D-2-HG.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC12297413 | PMC |
| http://dx.doi.org/10.1038/s41467-025-62225-8 | DOI Listing |
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