RT Journal Article
T1 The Q-junction and the inflammatory response are critical pathological and therapeutic factors in CoQ deficiency.
A1 Gonzalez-Garcia, Pilar
A1 Diaz-Casado, Maria Elena
A1 Hidalgo-Gutierrez, Agustin
A1 Jimenez-Sanchez, Laura
A1 Bakkali, Mohammed
A1 Barriocanal-Casado, Eliana
A1 Escames, Germaine
A1 Chiozzi, Riccardo Zenezini
A1 Völlmy, Franziska
A1 Zaal, Esther A
A1 Berkers, Celia R
A1 Heck, Albert J R
A1 Lopez, Luis C
K1 Coenzyme Q
K1 Mitochondrial disease
K1 Omics
K1 Phenolic compound
K1 Therapy
AB Defects in Coenzyme Q (CoQ) metabolism have been associated with primary mitochondrial disorders, neurodegenerative diseases and metabolic conditions. The consequences of CoQ deficiency have not been fully addressed, and effective treatment remains challenging. Here, we use mice with primary CoQ deficiency (Coq9R239X), and we demonstrate that CoQ deficiency profoundly alters the Q-junction, leading to extensive changes in the mitochondrial proteome and metabolism in the kidneys and, to a lesser extent, in the brain. CoQ deficiency also induces reactive gliosis, which mediates a neuroinflammatory response, both of which lead to an encephalopathic phenotype. Importantly, treatment with either vanillic acid (VA) or β-resorcylic acid (β-RA), two analogs of the natural precursor for CoQ biosynthesis, partially restores CoQ metabolism, particularly in the kidneys, and induces profound normalization of the mitochondrial proteome and metabolism, ultimately leading to reductions in gliosis, neuroinflammation and spongiosis and, consequently, reversing the phenotype. Together, these results provide key mechanistic insights into defects in CoQ metabolism and identify potential disease biomarkers. Furthermore, our findings clearly indicate that the use of analogs of the CoQ biosynthetic precursor is a promising alternative therapy for primary CoQ deficiency and has potential for use in the treatment of more common neurodegenerative and metabolic diseases that are associated with secondary CoQ deficiency.
PB Elsevier BV
YR 2022
FD 2022-07-10
LK http://hdl.handle.net/10668/22496
UL http://hdl.handle.net/10668/22496
LA en
NO González-García P, Díaz-Casado ME, Hidalgo-Gutiérrez A, Jiménez-Sánchez L, Bakkali M, Barriocanal-Casado E, et al. The Q-junction and the inflammatory response are critical pathological and therapeutic factors in CoQ deficiency. Redox Biol. 2022 Sep;55:102403.
DS RISalud
RD Apr 6, 2025