GFER

Growth factor, augmenter of liver regeneration (GFER) is also known as FAD-linked sulfhydryl oxidase ALR, which belongs to the Erv1/ALR family of proteins. This family can be found in higher and lower eukaryotes. There are two isoform of GFER: Isoform 1 and isoform 2. Isoform 2 missing 1 ¨C 80 aa. Isoform 1 is mainly located in mitochondrion intermembrane space, while Isoform 1 is secreted to cytoplasm. Isoform 1 of GFER regenerates the redox-active disulfide bonds in CHCHD4/MIA40, a chaperone essential for disulfide bond formation and protein folding in the mitochondrial intermembrane space. The reduced form of CHCHD4/MIA40 forms a transient intermolecular disulfide bridge with GFER/ERV1, resulting in regeneration of the essential disulfide bonds in CHCHD4/MIA40, while GFER/ERV1 becomes re-oxidized by donating electrons to cytochrome c or molecular oxygen. The isoform 2 of GFER may act as an autocrine hepatotrophic growth factor promoting liver regeneration.