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Citation
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.
FlyBase ID
FBrf0233960
Publication Type
Research paper
Abstract

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.

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

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

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Secondary IDs
    Language of Publication
    English
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Journal
    Abbreviation
    Nat. Commun.
    Title
    Nature communications
    ISBN/ISSN
    2041-1723
    Data From Reference
    Alleles (22)
    Genes (16)
    Human Disease Models (3)
    Cell Lines (2)
    Natural transposons (1)
    Insertions (10)
    Experimental Tools (4)
    Transgenic Constructs (20)