This report describes a fly model of mitochondrial complex IV deficiency related to the human genes SCO1 and SCO2. Both human genes are implicated in complex IV (COX) deficiency (MIM:604377, FBhh0001323; MIM:619048, FBhh0001324) both are nuclear genes that encode proteins that function in the mitochondria and are required for COX assembly. A single fly gene, Dmel\Scox, is orthologous to both SCO1 and SCO2. Multiple genetic reagents, including RNAi-targeting constructs, overexpression constructs, and alleles caused by insertional mutagenesis, have been generated for Dmel\Scox.
Neither human SCO1 nor SCO2 has been introduced into flies.
Loss-of-function alleles of Dmel\Scox are lethal, usually at the larval stage. By using targeted expression of UAS-RNAi constructs, it has been shown that cardiac-specific knockdown results in reduced lifespan, severely compromised heart function and structure, and dilated cardiomyopathy. Scox was one of two mitochondrial proteins identified in a mosaic analysis of essential genes for genes required for photoreceptor cell maintenance and photoresponse. Glial cell-specific knockdown of Scox results in locomotive dysfunction.
[updated Nov. 2021 by FlyBase; FBrf0222196]
Mitochondrial complex IV deficiency (cytochrome c oxidase deficiency) is clinically heterogeneous, ranging from isolated myopathy to severe multisystem disease, with onset from infancy to adulthood. [from MIM:220110; 2016.08.12]
The nuclear gene SCO1 (cytochrome c oxidase assembly) encodes a mitochondrial copper-binding protein that, together with SCO2, is involved in the biogenesis of the copper-containing CuA site in the MTCO2 subunit of cytochrome c oxidase (COX), the terminal component of the mitochondrial respiratory chain. [from MIM:603644; 2016.08.12]
Many to one: 2 human to 1 Drosophila; the second orthologous human gene is SCO2.
Many to one: 2 human to 1 Drosophila; the second human gene is SCO1.
High-scoring ortholog of human SCO1; moderate-scoring ortholog of human SCO2 (1 Drosophila to 2 human). Dmel\Scox shares 47-54% identity and 66-73% similarity with the human genes.
