Genetic mosaic analysis of a deleterious mitochondrial DNA mutation in Drosophila reveals novel aspects of mitochondrial regulation and function.
Bottom Line: In the present study, we found that the decrease in cytochrome c oxidase (COX) activity was ascribable to a temperature-dependent destabilization of cytochrome a heme.Using a genetic scheme that expresses a mitochondrially targeted restriction enzyme to induce tissue-specific homoplasmy in heteroplasmic flies, we found that mt:CoI(T300I) homoplasmy in the eye caused severe neurodegeneration at 29°C.Our results demonstrate a novel approach for Drosophila mtDNA genetics and its application in modeling mtDNA diseases.
Affiliation: Laboratory of Molecular Genetics, National Institutes of Health, Bethesda, MD 20892.Show MeSH
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Mentions: Homoplasmic mt:CoIT300I flies survived to adult stages when raised at 25°C but lived up to only 2 wk even at this permissive condition (Figure 2A). In addition, their mobility dropped quickly. By the age of 10 d, most mt:CoIT300I flies could hardly move (Figure 2B). mt:CoIT300I flies die within 5 d after being shifted to 29°C (Hill, Chen, et al., 2014), which prevents us from exploring age-related dysfunctions that are normally associated with mtDNA diseases. In addition, most human mtDNA diseases are caused by heteroplasmic mutations and affect specific tissues. We therefore turned to heteroplasmic flies to probe age-related and tissue-specific phenotypes of mt:CoIT300I at the restrictive condition.
Affiliation: Laboratory of Molecular Genetics, National Institutes of Health, Bethesda, MD 20892.