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Evidence of selection against damaged mitochondria during early embryogenesis in the mouse.
MACHADO, Thiago S.; MACABELLI, Carolina H.; DEL COLLADO, Maite Barrondo; MEIRELLES, Flávio Vieira; GUIMARÃES, Francisco Eduardo Gontijo; CHIARATTI, Marcos R.
Abstract: There is evidence of a purifying filter acting in the female germline to prevent the expansion of deleterious mutations in the mitochondrial DNA (mtDNA). Given our poor understanding of this filter, here we investigate the competence of the mouse embryo to eliminate dysfunctional mitochondria. Toward that, mitochondria were damaged by photoirradiation of NZB/BINJ zygotes loaded with chloromethyl-X-rosamine (CMXRos). The resultant cytoplasm was then injected into C57BL/6J zygotes to track the levels of NZB/BINJ mtDNA during the preimplantation development. About 30% of NZB/BINJ mtDNA was present after injection, regardless of using photoirradiated or non-photoirradiated cytoplasmic donors. Moreover, injection of photoirradiated-derived cytoplasm did not impact development into blastocysts. However, lower levels of NZB/BINJ mtDNA were present in blastocysts when comparing injection of photoirradiated (24.7% ± 1.43) versus non-photoirradiated (31.4% ± 1.43) cytoplasm. Given that total mtDNA content remained stable between stages (zygotes vs. blastocysts) and treatments (photoirradiated vs. non-photoirradiated), these results indicate that the photoirradiated-derived mtDNA was replaced by recipient mtDNA in blastocysts. Unexpectedly, treatment with rapamycin prevented the drop in NZB/BINJ mtDNA levels associated with injection of photoirradiated cytoplasm. Additionally, analysis of mitochondria-autophagosome colocalization provided no evidence that photoirradiated mitochondria were eliminated by autophagy. In conclusion, our findings give evidence that the mouse embryo is competent to mitigate the levels of damaged mitochondria, which might have implications to the transmission of mtDNA-encoded disease.
Frontiers in Genetics
v. 11, p. 762-1-762-9 - Ano: 2020
Fator de Impacto: 3,258
    @article={003000704,author = {MACHADO, Thiago S.; MACABELLI, Carolina H.; DEL COLLADO, Maite Barrondo; MEIRELLES, Flávio Vieira; GUIMARÃES, Francisco Eduardo Gontijo; CHIARATTI, Marcos R.},title={Evidence of selection against damaged mitochondria during early embryogenesis in the mouse},journal={Frontiers in Genetics},note={v. 11, p. 762-1-762-9},year={2020}}