The human gene OPA1 is implicated in multiple diseases with a broad range of neurologic phenotypes (OMIM:605290); common phenotypes include optic atrophy, other vision problems, hearing loss, and ataxia. The OPA1 gene encodes a protein that localizes to the inner mitochondrial membrane and that impacts mitochondrial fusion, apoptosis, reactive oxygen species production and ATP production. It has been postulated that retinal ganglion cells may be particularly vulnerable to mitochondrial dysfunction (Yu-Wai-Man et al., 2009; pubmed:19001017). There is a single orthologous gene in Drosophila, Dmel\Opa1, for which RNAi-targeting constructs and hypomorphic alleles caused by insertional mutagenesis have been generated.
The human OPA1 gene has not been introduced into flies.
Animals homozygous for loss-of-functions mutations of Dmel\Opa1 die in the larval stage. Heterozygotes exhibit visual abnormalities and defects in mitochondrial morphology in muscle. When targeted loss of function is effected by RNAi, fragmented mitochondria are frequently observed in the targeted tissue. Somatic clones, especially in the eye, have been used to further characterize loss-of-function phenotypes. Phenotypes of somatic clones and in heterozygous animals have been used to assess therapeutic candidates. Genetic and physical interactions of Dmel\Opa1 have been described; see below and in the Opa1 gene report.
[updated Oct. 2017 by FlyBase; FBrf0222196]
The OPA1 gene encodes a protein that localizes to the inner mitochondrial membrane and regulates several important cellular processes including stability of the mitochondrial network, mitochondrial bioenergetic output, and sequestration of proapoptotic cytochrome c oxidase molecules within the mitochondrial cristae spaces (summary by Yu-Wai-Man et al., 2010; pubmed:). [from OMIM:605290; 2017.10.02]