دورية أكاديمية
The Q-junction and the inflammatory response are critical pathological and therapeutic factors in CoQ deficiency.
| العنوان: | The Q-junction and the inflammatory response are critical pathological and therapeutic factors in CoQ deficiency. |
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| المؤلفون: | González-García P; Departamento de Fisiología, Facultad de Medicina, Universidad de Granada, 18016, Granada, Spain; Instituto de Biotecnología, Centro de Investigación Biomédica, Universidad de Granada, 18016, Granada, Spain., Díaz-Casado ME; Departamento de Fisiología, Facultad de Medicina, Universidad de Granada, 18016, Granada, Spain; Instituto de Biotecnología, Centro de Investigación Biomédica, Universidad de Granada, 18016, Granada, Spain., Hidalgo-Gutiérrez A; Departamento de Fisiología, Facultad de Medicina, Universidad de Granada, 18016, Granada, Spain; Instituto de Biotecnología, Centro de Investigación Biomédica, Universidad de Granada, 18016, Granada, Spain., Jiménez-Sánchez L; Ibs.Granada, 18016, Granada, Spain., Bakkali M; Departamento de Genética, Facultad de Ciencias, Universidad de Granada, 18071, Granada, Spain., Barriocanal-Casado E; GENYO, Centre for Genomics and Oncological Research, Genomic Medicine Department, Pfizer-University of Granada-Andalusian Regional Government, 18016, Granada, Spain., Escames G; Departamento de Fisiología, Facultad de Medicina, Universidad de Granada, 18016, Granada, Spain; Instituto de Biotecnología, Centro de Investigación Biomédica, Universidad de Granada, 18016, Granada, Spain., Chiozzi RZ; Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute of Pharmaceutical Sciences, Utrecht University, 3584CH, Utrecht, Netherlands; Netherlands Proteomics Centre, Padualaan 8, 3584 CH, Utrecht, the Netherlands., Völlmy F; Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute of Pharmaceutical Sciences, Utrecht University, 3584CH, Utrecht, Netherlands; Netherlands Proteomics Centre, Padualaan 8, 3584 CH, Utrecht, the Netherlands., Zaal EA; Netherlands Proteomics Centre, Padualaan 8, 3584 CH, Utrecht, the Netherlands; Division of Cell Biology, Metabolism & Cancer, Department of Biomolecular Health Sciences, Faculty of Veterinary Medicine, Utrecht University, 3508 TD, Utrecht, the Netherlands., Berkers CR; Netherlands Proteomics Centre, Padualaan 8, 3584 CH, Utrecht, the Netherlands; Division of Cell Biology, Metabolism & Cancer, Department of Biomolecular Health Sciences, Faculty of Veterinary Medicine, Utrecht University, 3508 TD, Utrecht, the Netherlands., Heck AJR; Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute of Pharmaceutical Sciences, Utrecht University, 3584CH, Utrecht, Netherlands; Netherlands Proteomics Centre, Padualaan 8, 3584 CH, Utrecht, the Netherlands., López LC; Departamento de Fisiología, Facultad de Medicina, Universidad de Granada, 18016, Granada, Spain; Instituto de Biotecnología, Centro de Investigación Biomédica, Universidad de Granada, 18016, Granada, Spain. Electronic address: luisca@ugr.es. |
| المصدر: | Redox biology [Redox Biol] 2022 Sep; Vol. 55, pp. 102403. Date of Electronic Publication: 2022 Jul 15. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier, B.V Country of Publication: Netherlands NLM ID: 101605639 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2213-2317 (Electronic) Linking ISSN: 22132317 NLM ISO Abbreviation: Redox Biol Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: [Amsterdam]: Elsevier, B.V., [2013]- |
| مستخلص: | 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 (Coq9 R239X ), 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. (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.) |
| فهرسة مساهمة: | Keywords: Coenzyme Q; Mitochondrial disease; Omics; Phenolic compound; Therapy |
| تواريخ الأحداث: | Date Created: 20220721 Latest Revision: 20231019 |
| رمز التحديث: | 20240628 |
| مُعرف محوري في PubMed: | PMC9301574 |
| DOI: | 10.1016/j.redox.2022.102403 |
| PMID: | 35863266 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 2213-2317 |
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| DOI: | 10.1016/j.redox.2022.102403 |