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Kandul, N.P., Zhang, T., Hay, B.A., Guo, M. (2016). Selective removal of deletion-bearing mitochondrial DNA in heteroplasmic Drosophila.  Nat. Commun. 7(): 13100.
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Research paper

Mitochondrial DNA (mtDNA) often exists in a state of heteroplasmy, in which mutant mtDNA co-exists in cells with wild-type mtDNA. High frequencies of pathogenic mtDNA result in maternally inherited diseases; maternally and somatically acquired mutations also accumulate over time and contribute to diseases of ageing. Reducing heteroplasmy is therefore a therapeutic goal and in vivo models in post-mitotic tissues are needed to facilitate these studies. Here we describe a transgene-based model of a heteroplasmic lethal mtDNA deletion (mtDNA(Δ)) in adult Drosophila muscle. Stimulation of autophagy, activation of the PINK1/parkin pathway or decreased levels of mitofusin result in a selective decrease in mtDNA(Δ). Decreased levels of mitofusin and increased levels of ATPIF1, an inhibitor of ATP synthase reversal-dependent mitochondrial repolarization, result in a further decrease in mtDNA(Δ) levels. These results show that an adult post-mitotic tissue can be cleansed of a deleterious genome, suggesting that therapeutic removal of mutant mtDNA can be achieved.

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PubMed Central ID
PMC5114534 (PMC) (EuropePMC)
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Personal communication to FlyBase

Kandul insertions.
Kandul and Hay, 2019.11.26, Kandul insertions. [FBrf0244534]

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    Nat. Commun.
    Nature communications
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    Alleles (22)
    Genes (16)
    Human Disease Models (3)
    Cell Lines (2)
    Natural transposons (1)
    Insertions (10)
    Experimental Tools (4)
    Transgenic Constructs (20)