Project description:MicroRNAs are amplifiers of monocyte inflammatory networks and repressors of metabolism Milk and blood isolated CD14+ monocyte cells taken from 5 infected Holstein friesians and 5 control Holstein friesians. Five animal infected with live S. uberis, cells extracted at 0, 12, 24, 36, and 48 hours post infection.
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.
Project description:The liver of dairy cows naturally displays a series of metabolic adaptation during the periparturient period in response to the increasing nutrient requirement of lactation. The hepatic adaptation is partly regulated by insulin resistance and it is affected by the prepartal energy intake level of cows. We aimed to investigate the metabolic changes in the liver of dairy cows during the periparturient at gene expression level and to study the effect of prepartal energy level on the metabolic adaptation at gene expression level.B13:N13
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.
