2025/11/01 by Parith Wongkittichote, Rachel M. Guerra, Daniel J. Wegner +4 · 1 voice
Biochemistry, Genetics and Molecular Biology · Energy · #Coenzyme Q10 studies and effects #Mitochondrial Function and Pathology #Metalloenzymes and iron-sulfur proteins
paper · pdf · doi:10.1002/jmd2.70038
openalex publication_date 2025/11/01 · openalex created_date 2025/11/05 · openalex updated_date 2026/07/28
ABSTRACT Coenzyme Q 10 (CoQ 10 ) is a coenzyme and antioxidant involved in multiple bioenergetic and biosynthetic processes, particularly within mitochondria. The biosynthesis of CoQ 10 is a tightly regulated process that involves multiple enzymes, including the methyltransferase COQ5. Genetic defects in COQ5 have recently been associated with autosomal recessive COQ5 ‐related primary CoQ 10 deficiency. The clinical manifestations of seven individuals previously reported were primarily neurological and ophthalmological. Here, we report two siblings with profound developmental delay and brain imaging consistent with multistage strokes. Clinical exome sequencing revealed compound heterozygous variants in COQ5 , including one frameshift deletion and one missense variant. Our functional complementation studies demonstrate that a Saccharomyces cerevisiae COQ5 ortholog harboring the corresponding missense variant fails to fully rescue coq5 ∆ CoQ 6 production, leading to the accumulation of CoQ biosynthetic intermediates. After the diagnosis, CoQ 10 supplementation was started on the proband, leading to subjective clinical improvement. We describe new cases of COQ5 ‐related primary CoQ 10 deficiency and expand the phenotypic and molecular spectrum of the disease. We also establish a yeast system to evaluate the effects of the variants in COQ5 and support the use of CoQ 10 supplementation for patients with COQ5 ‐related primary CoQ 10 deficiency.