A number of genes that encode components of mitochondrial complex II (succinate dehydrogenase, SDH) have been implicated in neuromuscular or multisystemic disease (see MIM:252011); SDHAF1, a gene required for assembly of complex II, has also been implicated in mitochondrial complex II dysfunction. Work in Drosophila has elucidated the role of another succinate dehydrogenase complex assembly factor, SDHAF4. Results of that work, using the Drosophila ortholog Sirup, indicate that SDHAF4 may also be implicated in neuromuscular disease caused by mitochondrial complex II dysfunction.
A UAS construct of the wild-type human Hsap\SDHAF4 gene has been introduced into flies. Partial heterologous rescue (functional complementation) has been observed for the bang-sensitivity loss-of-function phenotype of Dmel\Sirup. There is a second gene in Drosophila orthologous to Hsap\SDHAF4; that gene, CG15283, exhibits testis-specific or testis-biased expression.
Animals homozygous for amorphic mutations of Dmel\Sirup have a much-reduced adult lifespan and are sensitive to oxidative stress induced by hyperoxia. They exhibit multiple neural phenotypes, including bang sensitivity, disorganized retinal architecture, and photoreceptor defects.
[updated May 2019 by FlyBase; FBrf0222196]
Mitochondrial complex II deficiency is an autosomal recessive disorder with a highly variable phenotype. Some patients have multisystem involvement of the brain, heart, muscle, liver, and kidneys resulting in death in infancy, whereas others have only isolated cardiac or muscle involvement with onset in adulthood and normal cognition. [from MIM:252011; 2019.05.09]
One to many: 1 human to 2 Drosophila.
