Project description:We have used a Comparative Genomic Hybridization (CGH) microarray to determine the effects of mtDNA depletion using ddC on chromosome stability of Holstein cells that were used as the donor cells for embryo production by Somatic Cell Nuclear Transfer. The results showed that there is no duplications or deletions on chromosomes of mtDNA depleted cells when compared with that of non-depleted cells. In conclusion, depleting mtDNA by using ddC had no negative effect on chromosome stability in the donor cells.
Project description:Mito-nuclear crosstalk underlying ovarian aging remains elusive. Single-cell transcriptomics of aged ovaries identified senescent signatures including dysregulated mitochondrial metabolism, disturbed histone modification and enriched SASP. We demonstrated that impaired SIRT5-mediated desuccinylation drives ovarian aging. As a major substrate of SIRT5 in the TCA cycle, SUCLG2 is regulated by desuccinylation at K93 and K101, which enhances its stability and activity to rescue mitochondrial dysfunction. Conversely, SUCLG2 hypersuccinylation leads to acetyl-CoA accumulation, increases nuclear H4K8ac and upregulates metabolic genes to compensate for energy deficiency. In vivo experiments showed excess acetyl-CoA accelerates ovarian aging, while a SUCLG2 desuccinylation mutant alleviates this defect. This study reveals the molecular basis of ovarian aging and highlights the SIRT5-SUCLG2 axis as a promising therapeutic target.
