ArticleClinical and translational medicine2026
Glutathione peroxidase 3 preserves hepatocyte mitochondrial quality control to enhance macrophage pro-regenerative phenotype during liver regeneration.
Article in Clinical and translational medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundPrecise regulation of mitochondrial function is critical for liver regeneration. However, the underlying regulatory mechanism remains elusive. Here, we aimed to investigate the role of hepatocellular glutathione peroxidase 3 (GPX3) in liver regeneration.
methodsIn a 70% partial hepatectomy (PH) mouse model, immunostaining and single-cell RNA sequencing revealed significant enrichment but down-regulation of mitochondrial oxidative phosphorylation pathways post-PH, along with up-regulated hypoxia-inducible factor 1a (HIF-1a) and GPX3 in hepatocytes. Single-cell analysis confirmed peak GPX3 expression in hepatocytes at day 2 post-PH. Hepatocyte-specific GPX3 knockout impaired mitochondrial function and delayed liver regeneration.
resultsMechanistically, immunoprecipitation-mass spectrometry and MitoCarta3.0 analysis identified voltage-dependent anion channel 1 (VDAC1) as a direct GPX3-binding partner. GPX3 interacted with VDAC1 via its A2 domain (residues 75-150), suppressing VDAC1 oligomerisation to restore mitochondrial Ca
conclusionsIn conclusion, GPX3 promotes liver regeneration by inhibiting VDAC1 oligomerisation to stabilise mitochondrial Ca KEY POINTS: GPX3 directly binds VDAC1 via its A2 domain to suppress VDAC1 oligomerisation, restoring mitochondrial Ca
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