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4-Hydroxybenzoic acid restores CoQ10 biosynthesis in human COQ2 deficiency.

ABSTRACT: The clinical phenotypes of human CoQ10-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 CoQ10-biosynthesis in COQ2-deficient cell lines. This was accompanied by increased protein expression of CoQ10-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.

SUBMITTER: Herebian D

PROVIDER: S-EPMC5740244 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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4-Hydroxybenzoic acid restores CoQ10 biosynthesis in human COQ2 deficiency.

Herebian Diran D Seibt Annette A Smits Sander H J SHJ Rodenburg Richard J RJ Mayatepek Ertan E Distelmaier Felix F

Annals of clinical and translational neurology 20171017 12

The clinical phenotypes of human CoQ10-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 CoQ10-biosynthesis in COQ2-deficient cell lines. This was accompanied by increased protein expression of CoQ10-biosynthesis-enzymes as well as a rescue of c ...[more]

PMID: 29296619

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