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Nucleoside-Diphosphate Kinase 1 and 2 are master regulators of a liver protective response to high fat diet [RNA-seq]

ABSTRACT: Nucleoside-Diphosphate Kinase 1 and 2 are master regulators of a liver protective response to high fat diet [RNA-seq]

PROVIDER: PRJNA816471 | ENA |

REPOSITORIES: ENA

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Nucleoside-Diphosphate Kinase 1 and 2 are master regulators of a liver protective response to high fat diet.

Project description:Nucleoside-Diphosphate Kinase 1 and 2 are master regulators of a liver protective response to high fat diet.

| PRJNA816457 | ENA

Nucleoside-Diphosphate Kinase 1 and 2 are master regulators of a liver protective response to high fat diet [ChIP-seq]

Project description:Nucleoside-Diphosphate Kinase 1 and 2 are master regulators of a liver protective response to high fat diet [ChIP-seq]

| PRJNA816470 | ENA

Nucleoside-Diphosphate Kinase 1 and 2 are master regulators of a liver protective response to high fat diet [ChIP-seq]

Project description:Fatty acid homeostasis is critical for normal cellular physiology and leads to severe diseases when deregulated. Here we report Nucleoside-Diphosphate Kinase 1 and 2 (NME1/2) as major cellular co-enzyme A (CoA) and acetyl-CoA binding proteins and negative regulators of de novo lipogenesis (DNL). Structural studies demonstrate that Nme1 recognizes CoA through its nucleotide moiety, which competes for binding with ADP/ATP. By using a Nme2 ko mouse model, we observe that NME2 is required for the gene transcriptional response to a high fat diet (HFD) in liver cells, leading to a repression of lipogenesis and the activation of a protective gene response. Nme2 ko mice submitted to a HFD challenge are unable to repress key lipogenic genes, resulting in an excessive triglyceride synthesis and liver steatosis. Mechanistically, the NME2-dependent down-regulation of DNL in response to HFD changes the balance for the use of acetyl-CoA between the competing paths of acetylation and DNL, thereby increasing TSS-targeted histone acetylation and gene activation. A structure-guided generation of a NME1 mutant, with intact NDK activity, but unable to bind CoA, directly demonstrates the functional impact of acetyl-CoA/CoA binding by NME1/2 in repressing DNL. Taken together, these findings highlight a yet unknow protective liver response to HFD, regulated by multi-ligand binding proteins which act as direct sensors for the cellular levels of NDP/NTP and CoA/acetyl-CoA.

2023-08-01 | GSE198687 | GEO

Nucleoside-Diphosphate Kinase 1 and 2 are master regulators of a liver protective response to high fat diet [RNA-seq]

2023-08-01 | GSE198686 | GEO

Nucleoside-Diphosphate Kinase 1 and 2 (Nme1/2) are major cellular co-enzyme A/acetyl-CoA binding factors

Project description:Co-enzyme A is the essential cellular carrier of the acetyl group, largely used in fatty acid synthesis and lysine post-translational modifications of proteins. Following the analysis of the cellular CoA-binding proteome, we identified Nme1/2 as major abundant cytoplasmic CoA-binding proteins. We report a novel mechanism that controls fatty acids synthesis involving ATP-dependent acetyl-CoA binding by Nucleoside Diphosphate Kinases 1 and 2 (Nme1/2).

2023-08-01 | PXD029159 | Pride

Nucleoside-Diphosphate Kinase 1 and 2 are master regulators of a liver protective response to high fat diet.

Project description:This SuperSeries is composed of the SubSeries listed below.

2023-08-01 | GSE198688 | GEO

Knockdown of the nucleoside diphosphate linked moiety X-type motif Nudt19 increases fatty acid oxidation and ATP production in murine liver cells

Project description:Changes in intracellular CoA levels are known to contribute to the development of non-alcoholic fatty liver disease (NAFLD) in type 2 diabetes (T2D). The underlying genetic basis for the development and progression of these complex disorders, however, is still poorly understood. Due to their diverse susceptibility towards metabolic diseases, mouse inbred strains have been proven to serve as powerful tools in the identification of novel genetic factors that are fundamental in the pathophysiology of diabetes and NAFLD. Transcriptome analysis revealed the nucleoside diphosphate linked moiety X type motif Nudt19 as novel candidate gene responsible for NAFLD and T2D development. Knockdown (KD) of Nudt19 increased both mitochondrial and glycolytic ATP production rates in Hepa 1-6 cells. The enforced utilization of glutamine or fatty acids as energy substrate reduced uncoupled respiration in NT cells. This reduction was prevented upon knockdown of Nudt19. Furthermore, incubation with palmitate or oleate increased mitochondrial ATP production and uncoupled respiration in Nudt19 KD cells, but not in NT cells. The enhanced fatty acid oxidation in Nudt19 KD cells was accompanied by an increased abundance of Pdk4. This study describes for the first time Nudt19 as regulator of hepatic lipid metabolism and potential mediator of NAFLD and T2D development.

2022-04-11 | GSE186106 | GEO

Regulators of mitonuclear balance link mitochondrial metabolism to mtDNA expression

Project description:Mitochondrial oxidative phosphorylation (OXPHOS) complexes are assembled from proteins encoded by both nuclear and mitochondrial DNA. These dual-origin enzymes pose a complex gene regulatory challenge for cells requiring coordinated gene expression across organelles. To identify genes involved in dual-origin protein complex synthesis, we performed fluorescence-activated cell-sorting-based genome-wide screens analysing mutant cells with unbalanced levels of mitochondrial- and nuclear-encoded subunits of Complex IV. We identified genes involved in OXPHOS biogenesis, including two uncharacterized genes: PREPL and NME6. We found that PREPL specifically impacts Complex IV biogenesis by acting at the intersection of mitochondrial lipid metabolism and protein synthesis, whereas NME6, an uncharacterized nucleoside diphosphate kinase, controls OXPHOS biogenesis through multiple mechanisms reliant on its NDPK domain. Firstly, NME6 forms a complex with RCC1L, which together perform nucleoside diphosphate kinase activity to maintain local mitochondrial pyrimidine triphosphate levels essential for mitochondrial RNA abundance. Secondly, NME6 modulates the activity of mitoribosome regulatory complexes, altering mitoribosome assembly and mitochondrial RNA pseudouridylation. Taken together, we propose that NME6 acts as a link between compartmentalized mitochondrial metabolites and mitochondrial gene expression.

2023-08-17 | GSE224503 | GEO

P-stalk ribosomes act as master regulators of cytokine-mediated processes

Project description:P-stalk ribosomes act as master regulators of cytokine-mediated processes

| PRJNA957309 | ENA

ChIP-seq of biofilm master regulators in four species of Candida

Project description:ChIP-seq of biofilm master regulators in four species of Candida

| PRJNA675631 | ENA