Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:1.3.5.1 (
succinate dehydrogenase
)
8,177
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Coenzyme Q10 (CoQ10) has an important role in mitochondrial energy metabolism by way of its functioning as an electron carrier in the respiratory chain. Genetic defects disrupting the endogenous biosynthesis pathway of CoQ10 may lead to severe metabolic disorders with onset in early childhood. Using exome sequencing in a child with fatal neonatal lactic acidosis and encephalopathy, we identified a homozygous loss-of-function variant in
COQ9
. Functional studies in patient fibroblasts showed that the absence of the
COQ9 protein
was concomitant with a strong reduction of COQ7, leading to a significant accumulation of the substrate of COQ7, 6-demethoxy ubiquinone10. At the same time, the total amount of CoQ10 was severely reduced, which was reflected in a significant decrease of mitochondrial respiratory chain succinate-cytochrome c oxidoreductase (
complex II
/III) activity. Lentiviral expression of
COQ9
restored all these parameters, confirming the causal role of the variant. Our report on the second
COQ9
patient expands the clinical spectrum associated with
COQ9
variants, indicating the importance of
COQ9
already during prenatal development. Moreover, the rescue of cellular CoQ10 levels and respiratory chain complex activities by CoQ10 supplementation points to the importance of an early diagnosis and immediate treatment.
...
PMID:Fatal neonatal encephalopathy and lactic acidosis caused by a homozygous loss-of-function variant in COQ9. 2608 41
