Project description:TMEM70 (transmembrane protein 70), a 21 kDa protein localized in the inner mitochondrial membrane, facilitates the biogenesis of mammalian F1Fo ATP synthase. Mutations of Tmem70 gene represent most frequent cause of isolated deficiency of human ATP synthase resulting in a severe, often fatal neonatal mitochondrial encephalo-cardiomyopathy. Contrary to humans, targeting of Tmem70 results in embryonic lethality in both mice and rats. In the current study, we tested effects of downregulation of the Tmem70 gene on gene transcription in the SHR (spontaneously hypertensive rat) heterozygotes.We performed gene expression profiling in the liver and found differentially expressed genes involved in innate imunity (RT1-T24-4, RT1-N3, RT1-CE5, Cd36, Marco, Socs3) and regulation of oxidative phosphorylation (Cdk1, Ccna2, Slc25a3).
Project description:Here we show that estrogen-related receptor γ (ERRγ) is an essential transcriptional coordinator of both renal mitochondrial and reabsorptive functions. ERRγ is highly and specifically expressed in the RECs, and its expression correlates with kidney function in humans. We generated REC-ERRγ KO mice which developed severe renal mitochondrial and reabsorptive dysfunction and fluid-filled cysts. Transcriptome and cistrome analysis revealed that ERRγ directly regulates mitochondrial metabolism and renal reabsorption. ChIP-reChIP-Seq studies further suggest that ERRγ employs a distinct mechanism to regulate renal reabsorption genes through functional cooperation with hepatic nuclear factor 1 beta (HNF1β), mutations of which cause strikingly similar renal dysfunction and cysts in humans and animals. Together these findings reveal a novel role for ERRγ in simultaneously coordinating a transcriptional program for renal energy production via mitochondria and energy consumption to perform reabsorptive functions required for normal kidney function
2018-04-25 | GSE104905 | GEO
Project description:Investigating low frequency somatic mutations in Arabidopsis with Duplex Sequencing
| PRJNA1065470 | ENA
Project description:Fragment Enrichment of Circulating Tumor DNA with Low-Frequency Mutations
Project description:Electrical pulse stimulation (EPS) is used to study exercise-related adaptations in muscle cells in vitro. We compared the effects of two EPS protocols: 1. intermittent high-frequency or 2. continuous low-frequency stimulation, on glucose and fatty acid metabolism, muscle fiber-type markers, mitochondrial proteins, myokines and extracellular vesicles (EV) release. Both EPS protocols enhanced post-exercise glycogen synthesis, while an increase in oxidative capacity was observed only after the intermittent high-frequency stimulation. Both EPS protocols increased GDF11 protein and release of EVs, which were characterized by transmission electron microscopy, nanoparticle tracking analysis and proteomics.
Project description:Studying whether removal of base-excision repair from mitochondria will result into increase in mitochondrial DNA (mtDNA) mutation load. The endogenous genes of OGG1 and MUTYH DNA glycosylases were modified to lack the genomic region encoding for the predicted mitochondrial targeting sequence. The mouse lines used: A mouse line that lacks the region encoding for the mitochondrial targeting sequence (L2 to W23) of OGG1 (Ogg1 dMTS mice). A mouse line that lacks the region encoding the mitochondrial targeting sequence (K2 to P33) of MUTYH (Mutyh dMTS mice). To accumulate mutations to the mitochondrial DNA these mice were bred double homozygous Mutyh dMTS x Ogg1 dMTS mice as a maternal lineage for five consecutive generations and mitochondrial DNA from liver was extracted from the offspring and sequenced with Illumina. OGG1 and MUTYH are involved in repair of 8-oxo-dG from DNA. 8-oxo-dG can be a mutagenic lesion because some DNA repair polymerases are known to erroneously incorporate adenosine opposite to 8-oxo-dG during replication leading to GC>TA transversion mutations.
Project description:To study whether increase in mitochondrial oxidative stress (SOD2 removal) and decrease in mitochondrial DNA repair (Ogg1 dMTS) results into increase in mitochondrial DNA mutation load. Oxidative stress has been suggested to induce mutations in mtDNA. To verify this, we extracted and sequenced (Illumina) mitochondrial DNA from heart Sod2 knockout animals that were also deficient for mitochondrial base-excision repair. The repair deficiency was induced by removing the genomic region encoding for the predicted mitochondrial targeting sequence from endogenous OGG1 (L2 to W23) called Ogg1 dMTS mice, thus excluding the protein from mitochondria. OGG1 is a DNA glycosylase that recognizes and repairs 8-oxo-dG damage from DNA. Oxidative stress can induce 8-oxo-dG lesions, thus we removed the mitochondrial matrix localized superoxide dismutase (SOD2) from these mice to increase the level of oxidative stress. 8-oxo-dG lesion can be mutagenic because some DNA repair polymerases are known to erroneously incorporate adenosine opposite to 8-oxo-dG during replication leading to GC>TA transversion mutations.