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Selective removal of deletion-bearing mitochondrial DNA in heteroplasmic Drosophila
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 (mtDNAΔ) in adult
Drosophila muscle. Stimulation of autophagy, activation of the PINK1/parkin pathway or decreased
levels of mitofusin result in a selective decrease in mtDNAΔ. Decreased levels of mitofusin and
increased levels of ATPIF1, an inhibitor of ATP synthase reversal-dependent mitochondrial repolarization,
result in a further decrease in mtDNAΔ 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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http://www.nature.co...les/ncomms13100
and a popular article:
"Have Caltech Scientists Figured Out How to Turn Back the Aging Clock?"
http://www.pasadenan...he-aging-clock/
