@misc{10481/93548,
year = {2024},
month = {5},
url = {https://hdl.handle.net/10481/93548},
abstract = {Coenzyme Q (CoQ) deficiency syndrome is conventionally treated with limited efficacy using exogenous
CoQ10. Poor outcomes result from low absorption and bioavailability of CoQ10 and the clinical heterogenicity
of the disease. Here, we demonstrate that supplementation with 4-hydroxybenzoic acid (4HB), the precursor
of the benzoquinone ring in the CoQ biosynthetic pathway, completely rescues multisystemic disease and
perinatal lethality in a mouse model of CoQ deficiency. 4HB stimulates endogenous CoQ biosynthesis in tissues
of Coq2 mutant mice, normalizing mitochondrial function and rescuing cardiac insufficiency, edema,
and neurodevelopmental delay. In contrast, exogenous CoQ10 supplementation falls short in fully restoring
the phenotype. The treatment is translatable to human use, as proven by in vitro studies in skin fibroblasts
from patients with pathogenic variants in COQ2. The therapeutic approach extends to other disorders characterized
by deficiencies in the production of 4HB and early steps of CoQ biosynthesis and instances of secondary
CoQ deficiency.},
organization = {Grant PID2021-126788OBI00
from the MICIU/AEI/10.13039/501100011033, Spain, and the ERDF/EU},
organization = {Grant MDA-602322 from the Muscular Dystrophy Association},
organization = {Grant PEER-0083-2020 from the Junta de Andalucía},
organization = {Consejería de Salud, Junta de Andalucía, Spain},
organization = {‘‘Margarita Salas program’’ from the Ministerio de Universidades, Spain},
organization = {University of Granada},
organization = {‘‘FPU program’’ from the Ministerio de Universidades, Spain},
organization = {DOD grant W81XWH2010807},
organization = {NIH grants R21AG077243-01A1 and 1R01NS134902-01},
organization = {Unit of Excellence ‘‘UNETE’’ from the University of Granada (UCEPP2017-05)},
publisher = {Elsevier},
title = {4-Hydroxybenzoic acid rescues multisystemic disease and perinatal lethality in a mouse model of mitochondrial disease},
doi = {10.1016/j.celrep.2024.114148},
author = {Corral Sarasa, Julia and Martínez Gálvez, Juan Manuel and González García, Pilar and Wendling, Olivia and Jiménez Sánchez, Laura and López Herrador, Sergio and Quinzii, Catarina M. and Díaz Casado, María Elena and López García, Luis Carlos},
}