Fumarylacetoacetate hydrolase domain-containing protein 1 (FAHD1)

Fumarylacetoacetate hydrolase domain-containing protein 1 (FAHD1) is a 24-kDa mitochondrial enzyme encoded by the FAHD1 gene. It belongs to the fumarylacetoacetate hydrolase superfamily and displays bifunctional enzymatic activities: oxaloacetate decarboxylase (ODx), which catalyzes the conversion of oxaloacetate (OAA) to pyruvate and CO₂, and acylpyruvate hydrolase (ApH), which hydrolyzes acetylpyruvate and fumarylpyruvate[1][3][6][9]. FAHD1 is a key regulator of mitochondrial metabolism, modulating cellular energy production by regulating OAA levels, TCA cycle flux, and ROS production, thereby impacting cell proliferation, senescence, and survival[2][5][7]. FAHD1's expression is tissue-dependent (kidney, liver) and is implicated in various pathophysiological states, including cancer and reproductive disorders[5][7]. Its structure consists of a conserved catalytic center shared within the superfamily, with species-specific sequence variability enabling selective antibody recognition and post-translational regulatory modifications[1][9]. If more structural, ligand, or inhibitor information becomes available, FAHD1 may emerge as a direct pharmacological target for diseases related to mitochondrial dysfunction or metabolic imbalance.

Other names

FAHD1C16orf36YISKLOxaloacetate decarboxylaseAcylpyruvase FAHD1Fumarylacetoacetate hydrolase domain-containing protein 1OAA decarboxylaseODxYisK-like proteinFLJ36880 protein

For in-development therapeutics, likely inhibition or modulation of FAHD1’s oxaloacetate decarboxylase activity, affecting mitochondrial OAA levels, TCA cycle flux, and ROS production