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Fig. 8
Schematic diagram of potential mechanisms that D-2-HG involved in liver regeneration in BA patients.
Biliary atresia is incurable and needs liver transplantation. Using targeted metabolomics, we unexpectedly identified a metabolite 2-hydroxyglutarate (2-HG) that has great potential in diagnosis or newborn screening. By using ?mini organs of liver? in vitro and a zebrafish model in vivo, we demonstrate D-2-HG accumulates in the liver and alters the hepatic microenvironment, and subsequently impairs liver regeneration via reducing the mitochondrial respiration and ATP synthase. Our findings reveal D-2-HG has a novel pathogenic mechanism that could have important diagnostic and therapeutic implications.
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Full text @ Cell Death Dis.