Coenzyme Q deficiency disease has a range of phenotypes, one of which is renal failure (see MIM:607426). This aspect of the disease has been investigated in Drosophila using genes that encode proteins in the biosynthetic pathway for CoQ. CoQ (also known as ubiquinone) serves as a redox carrier in the mitochondrial respiratory chain. Most work in flies has been done with Dmel\Coq2, for which classical amorphic and hypomorphic alleles, RNAi-targeting constructs, and an allele caused by insertional mutagenesis have been generated.
Multiple UAS constructs of human Hsap\COQ2 have been introduced into flies, including wild-type and a variant associated with coenzyme Q deficiency disease. Heterologous rescue (functional complementation) has been demonstrated for the reduced ANF-RFP uptake phenotype effected by nephrocyte-specific RNAi against Dmel\Coq2. The disease-associated variant fails to rescue. Variant(s) implicated in human disease tested (as transgenic human gene, COQ2): the S146N variant form has been introduced into flies.
RNAi-mediated knockdown of Coq2, Coq6, or Coq8 gene expression in nephrocytes results in significantly reduced uptake of an ANF-RFP marker protein relative to control nephrocytes. Additional characterization of nephrocytes in Coq2 knockdowns revealed abnormal nephrocyte slit diaphragms, increased numbers of mitochondria, and dysmorphic mitochondria; increased autophagy and mitophagy are observed. These phenotypes can be rescued by dietary CoQ supplementation.
Animals homozygous for loss-of-function mutations of Dmel\Coq2 typically die during the early larval stage; they are significantly smaller than wild-type. Heterozygous animals survive to adulthood and exhibit an increased lifespan.
[updated Jul. 2018 by FlyBase; FBrf0222196]
[COENZYME Q10 DEFICIENCY, PRIMARY, 1; COQ10D1](https://omim.org/entry/607426)
[COENZYME Q2, POLYPRENYLTRANSFERASE; COQ2](https://omim.org/entry/609825)
Coenzyme Q10 deficiency has been associated with 5 major forms or phenotypes: an encephalomyopathic form with seizures and ataxia; a multisystem infantile form with encephalopathy, cardiomyopathy and renal failure; a predominantly cerebellar form with ataxia and cerebellar atrophy; Leigh syndrome with growth retardation; and an isolated myopathic form. [from MIM:607426; 2018.07.06]
Primary CoQ10 deficiency is a rare, clinically heterogeneous autosomal recessive disorder caused by mutation in any of the genes encoding proteins directly involved in the synthesis of coenzyme Q10 (ubiquinone). [from MIM:607426; 2018.07.06]
Coenzyme Q10 is the predominant form in human; Coenzyme Q9 is the predominant form in insects. The COQ1 biosynthesis gene defines the length of the polyisoprene tail of CoQ and, because this gene differs between species, each organism presents a different repertoire of CoQ isoforms (FBrf0225872).
COQ2, or parahydroxybenzoate-polyprenyltransferase, catalyzes one of the final reactions in the biosynthesis of CoQ10. [from MIM:609825; 2018.07.06]
One to one: 1 human to 1 Drosophila
High-scoring ortholog of human COQ2 (1 Drosophila to 1 human). Dmel\Coq2 shares 63% identity and 76% similarity with the human gene.
High-scoring ortholog of human COQ6 (1 Drosophila to 1 human). Dmel\CG7277 shares 42% identity and 56% similarity with the human gene.
High-scoring ortholog of human COQ8A and COQ8B (1 Drosophila to 2 human). Dmel\Coq8 shares 50-52% identity and 68-69% similarity with the human genes.
