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Ubiquitin-mediated mitophagy regulates the inheritance of mitochondrial DNA mutations
Ubiquitin-controlled removal of damaged mitochondria affects how mutated mitochondrial DNA is passed on
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Abstract
Purifying selection of a mouse mtDNA mutation is observed during the maternal-zygotic transition.
- Mitochondrial DNA mutates approximately 15 times faster than nuclear DNA, complicating their cooperative function.
- Inhibition studies indicate that increased mitochondrial autophagy is linked to the purifying selection of mtDNA mutations.
- A high burden of mtDNA mutations, or heteroplasmy, disrupts the ubiquitin-proteasome system, allowing mutations to escape quality control.
- Inhibiting USP30 enhances mitophagy, which may lower mutant mtDNA levels in cells with high heteroplasmy.
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