Open Access4‐Hydroxybenzoic acid restores CoQ 10 biosynthesis in human COQ 2 deficiency
Author(s) -
Herebian Diran,
Seibt Annette,
Smits Sander H. J.,
Rodenburg Richard J.,
Mayatepek Ertan,
Distelmaier Felix
Publication year - 2017
Publication title -
annals of clinical and translational neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.824
H-Index - 42
ISSN - 2328-9503
DOI - 10.1002/acn3.486
Subject(s) - in silico , biosynthesis , medicine , phenotype , atp binding cassette transporter , biochemistry , pharmacology , enzyme , biology , gene , transporter
The clinical phenotypes of human CoQ 10 ‐deficiency caused by COQ2 mutations range from fatal neonatal disease to adult‐onset multisystem atrophy. So far, treatment options for these diseases are unsatisfactory. Here, we demonstrate that supplementation of 4‐hydroxybenzoic acid (4‐HBA) fully restores endogenous CoQ 10 ‐biosynthesis in COQ2‐deficient cell lines. This was accompanied by increased protein expression of CoQ 10 ‐biosynthesis‐enzymes as well as a rescue of cell viability during stress conditions. In silico analysis suggested a ligand transportation path for 4‐HBA through the COQ2 protein towards the mitochondrial matrix side. This process is apparently hindered by disease‐causing mutations, which can be overcome by increasing 4‐HBA concentrations.