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Mitochondrial DNA segregation and replication restrict the transmission of detrimental mutation.


ABSTRACT: Although mitochondrial DNA (mtDNA) is prone to accumulate mutations and lacks conventional DNA repair mechanisms, deleterious mutations are exceedingly rare. How the transmission of detrimental mtDNA mutations is restricted through the maternal lineage is debated. Here, we demonstrate that mitochondrial fission, together with the lack of mtDNA replication, segregate mtDNA into individual organelles in the Drosophila early germarium. After mtDNA segregation, mtDNA transcription begins, which activates respiration. Mitochondria harboring wild-type genomes have functional electron transport chains and propagate more vigorously than mitochondria containing deleterious mutations in hetreoplasmic cells. Therefore, mtDNA expression acts as a stress test for the integrity of mitochondrial genomes and sets the stage for replication competition. Our observations support selective inheritance at the organelle level through a series of developmentally orchestrated mitochondrial processes. We also show that the Balbiani body has a minor role in mtDNA selective inheritance by supplying healthy mitochondria to the pole plasm. These two mechanisms may act synergistically to secure the transmission of functional mtDNA through Drosophila oogenesis.

SUBMITTER: Chen Z 

PROVIDER: S-EPMC7337505 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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Mitochondrial DNA segregation and replication restrict the transmission of detrimental mutation.

Chen Zhe Z   Wang Zong-Heng ZH   Zhang Guofeng G   Bleck Christopher K E CKE   Chung Dillon J DJ   Madison Grey P GP   Lindberg Eric E   Combs Christian C   Balaban Robert S RS   Xu Hong H  

The Journal of cell biology 20200701 7


Although mitochondrial DNA (mtDNA) is prone to accumulate mutations and lacks conventional DNA repair mechanisms, deleterious mutations are exceedingly rare. How the transmission of detrimental mtDNA mutations is restricted through the maternal lineage is debated. Here, we demonstrate that mitochondrial fission, together with the lack of mtDNA replication, segregate mtDNA into individual organelles in the Drosophila early germarium. After mtDNA segregation, mtDNA transcription begins, which acti  ...[more]

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