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Mitochondrial fusion increases the mitochondrial DNA copy number in budding yeast.

Genes Cells. 2011 May;16(5):527-44. doi:10.1111/j.1365-2443.2011.01504.x. Epub 2011 Apr 05
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摘要


Mitochondrial fusion plays an important role in mitochondrial DNA (mtDNA) maintenance, although the underlying mechanisms are unclear. In budding yeast, certain levels of reactive oxygen species can promote recombination-mediated mtDNA replication, and mtDNA maintenance depends on the homologous DNA pairing protein Mhr1. Here, we show that the fusion of isolated yeast mitochondria, which can be monitored by the bimolecular fluorescence complementation-derived green fluorescent protein (GFP) fluorescence, increases the mtDNA copy number in a manner dependent on Mhr1. The fusion event, accompanied by the degradation of dissociated electron transport chain complex IV and transient reductions in the complex IV subunits by the inner membrane AAA proteases such as Yme1, increases levels. Analysis of the initial stage of mitochondrial fusion in early log-phase cells produced similar results. Moreover, higher duanyu1670 levels in mitochondrial fusion-deficient mutant cells increased the amount of newly synthesized mtDNA, resulting in increases in the mtDNA copy number. In contrast, reducing duanyu1670 levels in yme1 null mutant cells significantly decreased the mtDNA copy number, leading to an increase in cells lacking mtDNA. Our results indicate that mitochondrial fusion induces mtDNA synthesis by facilitating recombination-mediated replication and thereby prevents the generation of mitochondria lacking DNA.

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