Growth factor, augmenter of liver regeneration (GFER) (GFER)

Growth factor, augmenter of liver regeneration (GFER), also known as ALR or Erv1, is a FAD-dependent sulfhydryl oxidase primarily localized in the mitochondrial intermembrane space [1, 2]. It is a key component of the Mitochondrial Import and Assembly (MIA) pathway, where it works in tandem with Mia40 to facilitate the import and oxidative folding of cysteine-rich proteins [3, 5, 11]. Beyond its mitochondrial role, GFER acts as a hepatotrophic growth factor that promotes liver regeneration and protects hepatocytes from oxidative stress and apoptosis [1, 19, 22]. In clinical contexts, GFER is implicated in chronic liver diseases and various cancers; its downregulation is linked to the progression of nonalcoholic steatohepatitis (NASH), while its overexpression in certain tumors contributes to chemoresistance and immune evasion [14, 18, 20]. Recent studies identify GFER as a promising therapeutic target in pancreatic adenocarcinoma, where its inhibition disrupts mitochondrial redox homeostasis and enhances the efficacy of immune checkpoint inhibitors [12, 35]. Additionally, mutations in the GFER gene are associated with autosomal-recessive mitochondrial myopathy, highlighting its essential role in human health [3, 13].

Other names

ALRErv1HERV1HPOHPO1HPO2HSSHepatopoietinFAD-linked sulfhydryl oxidase ALREssential for respiration and vegetative growth protein 1

Inhibition of sulfhydryl oxidase activity leading to disruption of mitochondrial protein import and redox homeostasis