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How mothers give the best and enough mitochondria

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Air date: Friday, October 12, 2018, 12:00:00 PM
Time displayed is Eastern Time, Washington DC Local
Views: Total views: 162, (86 Live, 76 On-demand)
Category: NIH Director's Seminars
Runtime: 00:47:03
Description: NIH Directors Seminar Series

Dr. Xu’s Laboratory of Molecular Genetics, Systems Biology Center, NHLBI is interested in the basic mechanism guiding the transmission of our second genome- mitochondrial DNA. Mutations in mitochondrial genome have emerged as important factors compromising human health. Although mitochondrial genome is prone to accumulating mutations due to the high spontaneous mutation frequency and a lack of repair mechanisms, the crippling mitochondrial mutation is exceedingly rare in populations. It is puzzling how mothers are able to restrict the transmission of damaging mutations to the next generation. To overcome the unusual mitochondrial genetic system that features uniparental inheritance, polyploidy and amitotic segregation, Dr. Xu’s Lab has developed various tools to approach mitochondrial genome.

Dr. Xu’s Lab found that healthy mitochondria containing wild type genome propagate much more rigorously, and out-compete defective ones afflicted by damaging mutations in the female germ line. The model of replication competition based on the integrity of individual genomes explains the strong purifying selection observed in human and other animal models, and challenges the existing dogma known as bottleneck inheritance as an effective mean to prevent the accumulation of mtDNA mutations. Dr. Xu’s work also revealed a translation boost on the mitochondrial surface to facilitate the synthesis and import of nuclear encoded mitochondrial protein. This local translation coordinates the activities of both nuclear and mitochondrial genomes to support of biogenies if millions of mitochondria in developing oocytes to power the early embryonic development. More importantly, the local translation is sensitive to the fitness of individual mitochondrion, and allows the selective propagation of healthy organelles that underlies the selective inheritance.
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Author: Hong Xu, Ph.D., Senior Investigator, Laboratory of Molecular Genetics, NHLBI, NIH
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CIT Live ID: 28747
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