FAD-linked sulfhydryl oxidase, mitochondrial (GFER)

FAD-linked sulfhydryl oxidase, mitochondrial, also known as Augmenter of Liver Regeneration (ALR) or GFER, is a multifunctional enzyme localized primarily in the mitochondrial intermembrane space. It is a central component of the Mitochondrial Intermembrane Space Import and Assembly (MIA) pathway, where it catalyzes the oxidation of Mia40, enabling the oxidative folding and entrapment of cysteine-rich proteins imported into the mitochondria (UniProt P55789). Beyond its role in mitochondrial biogenesis, GFER acts as a potent hepatotrophic growth factor that stimulates liver regeneration and exerts anti-apoptotic effects on hepatocytes through the activation of signaling pathways such as MAPK/ERK (PubMed: 22434774). In clinical contexts, GFER deficiency is linked to severe mitochondrial myopathy and lactic acidosis, while its dysregulation is associated with chronic liver diseases and the progression of hepatocellular carcinoma (NCBI Gene ID: 2621). Its therapeutic potential is being explored in the context of treating liver failure and mitigating mitochondrial dysfunction in metabolic and neurodegenerative disorders.

Other names

Augmenter of liver regenerationALRGrowth factor Erv1-likeHepatopoietinHPOSulfhydryl oxidase GFERERV1 homolog

Administration of recombinant protein to stimulate hepatocyte proliferation and provide cytoprotection; modulation of the mitochondrial disulfide relay system to restore proteostasis.