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RNA sequencing of PTEN,Rb1 double knockout (DKO) mouse prostate organoids treated with vehicle or the small molecule mitochondrial pyruvate carrier (MPC) inhibitor UK5099

ABSTRACT: RNA sequencing of PTEN,Rb1 double knockout (DKO) mouse prostate organoids treated with vehicle or the small molecule mitochondrial pyruvate carrier (MPC) inhibitor UK5099

PROVIDER: PRJNA912597 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR22746475.fastq.gz	Fastqsanger.gz
	SRR22746476.fastq.gz	Fastqsanger.gz
	SRR22746477.fastq.gz	Fastqsanger.gz
	SRR22746478.fastq.gz	Fastqsanger.gz
	SRR22746479.fastq.gz	Fastqsanger.gz

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RNA sequencing of PTEN,Rb1 double knockout (DKO) mouse prostate organoids treated with vehicle or the small molecule mitochondrial pyruvate carrier (MPC) inhibitor UK5099

Project description:The goal of this study was to determine how pharmacological inhibition of the mitochondrial pyruvate carrier (MPC) alters lineage identity in transformed prostate organoids. We isolated basal cells from PTEN,Rb1 floxed mouse prostates and infected with Cre recombinase to establish PTEN, Rb1 double knockout (DKO) mouse prostate organoids. We then treated the DKO organoids with vehicle or 10uM UK5099 for five days.

2023-09-01 | GSE221021 | GEO

RNA sequencing of Mpc1 floxed mouse prostate organoids transduced with RFP control or Cre virus and treated -/+ small molecule MPC inhibitor UK5099

Project description:The goal of this study was to determine how knockout or pharmacological inhibition of the mitochondrial pyruvate carrier (MPC) alters lineage identity in the prostate. We isolated basal cells from Mpc1 floxed mouse prostates and transduced with a control RFP virus or Cre recombinase virus. We then plated into organoid culture and treated with either vehicle or the small molecule MPC inhibitor UK5099 for one week.

2023-09-01 | GSE221022 | GEO

ATAC-sequencing of primary basal-derived mouse prostate organoids treated with vehicle, the mitochondrial pyruvate carrier inhibitor UK5099, or lactate supplementation

Project description:The goal of this study was to understand how the mitochondrial pyruvate carrier inhibitor,UK5099, and lactate supplementation alter chromatin accessibility in primary basal-derived mouse prostate organoids.

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Mitochondrial Pyruvate Carrier 1 (MPC1) enforces T cell homeostasis by enabling pyruvate oxidation in the mitochondria

Project description:The transporter which uptakes pyruvate into the mitochondria during pyruvate oxidation, called the Mitochondrial Pyruvate Carrier (MPC), was only recently identified. While the MPC has been studied in a variety of cell types, including cancer cells and stem cells, very little is known about the importance of MPC in immune cells. Here, we delete MPC from hematopoietic cells and measure its impact on T cell gene expression.

2020-04-27 | GSE122711 | GEO

Transcriptomic analysis of acute mitochondrial pyruvate carrier inhibition using UK5099 in ABL prostate cancer cells

Project description:ABL cells (derivative of LNCaP) were treated with 100µM UK5099 or vehicle (control) for 72 hours, at which time total RNA was collected and analyzed using RNA-sequencing

2018-11-11 | GSE114708 | GEO

Mitochondrial Pyruvate Carrier 1 (MPC1) promotes peripheral T cell quiescence through metabolic regulation of thymic development

2019-12-30 | GSE138718 | GEO

The mitochondrial pyruvate carrier regulates antitumor function and memory T cell differentiation

Project description:Effector CD8+ T cells engage glycolysis for both lactate fermentation and pyruvate oxidation, the latter requiring the mitochondrial pyruvate carrier (MPC). How mitochondrial pyruvate metabolism impacts T cell function and fate, remains incompletely understood. We found that genetic deletion of MPC drives CD8+ T cell differentiation towards a memory phenotype. Metabolic flexibility induced by MPC inhibition in a nutrient-rich environment allowed for increased acetyl-coenzyme-A production by glutamine and fatty acid oxidation. This correlated with histone acetylation and chromatin accessibility on pro-memory genes. However, in a nutrient-deprived tumor microenvironment, MPC is essential for sustaining lactate oxidation that limits the metabolic suppression of CD8+ T cell anti-tumor function. To optimally translate these findings, we used a small molecule MPC inhibitor to imprint a stable memory phenotype during chimeric antigen receptor (CAR) T manufacturing, and demonstrated that infusing metabolically conditioned MPC WT CAR T cells resulted in superior and long-lasting anti-tumor activity.

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Transcriptomic analysis of acute mitochondrial pyruvate carrier inhibition using UK5099 in ABL prostate cancer cells

Project description:Transcriptomic analysis of acute mitochondrial pyruvate carrier inhibition using UK5099 in ABL prostate cancer cells

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UK5099 Inhibits the NLRP3 Inflammasome Independently of its Long-Established Target Mitochondrial Pyruvate Carrier.

Project description:Targeting NLRP3 inflammasome has been recognized as a promising therapeutic strategy for the treatment of numerous common diseases. UK5099, a long-established inhibitor of mitochondrial pyruvate carrier (MPC), is previously found to inhibit macrophage inflammatory responses independent of MPC expression. However, the mechanisms by which UK5099 inhibit inflammatory responses remain unclear. Here, it is shown that UK5099 is a potent inhibitor of the NLRP3 inflammasome in both mouse and human primary macrophages. UK5099 selectively suppresses the activation of the NLRP3 but not the NLRC4 or AIM2 inflammasomes. Of note, UK5099 retains activities on NLRP3 in macrophages devoid of MPC expression, indicating this inhibitory effect is MPC-independent. Mechanistically, UK5099 abrogates mitochondria-NLRP3 interaction and in turn inhibits the assembly of the NLRP3 inflammasome. Further, a single dose of UK5099 persistently reduces IL-1β production in an endotoxemia mouse model. Importantly, structure modification reveals that the inhibitory activities of UK5099 on NLRP3 are unrelated to the existence of the activated double bond within the UK5099 molecule. Thus, this study uncovers a previously unknown molecular target for UK5099, which not only offers a new candidate for the treatment of NLRP3-driven diseases but also confounds its use as an MPC inhibitor in immunometabolism studies.

| S-EPMC11434118 | biostudies-literature

RNA sequencing of mouse basal-derived prostate organoids treated with vehicle, UK5099, Butyrate, or UK5099+Butyrate

Project description:The goal of this study was to perform transcriptomics on vehicle-, UK5099-, Butyrate-, and UK5099+Butyrate-treated mouse prostate organoids. We used FACS to isolate basal cells from C57BL/6 mouse prostates and treated with small molecules for one week before harvesting for RNA-sequencing.

2023-09-01 | GSE236573 | GEO

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