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

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

PROVIDER: PRJNA506052 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR8207900.fastq.gz	Fastqsanger.gz
	SRR8207910.fastq.gz	Fastqsanger.gz
	SRR8207901.fastq.gz	Fastqsanger.gz
	SRR8207911.fastq.gz	Fastqsanger.gz
	SRR8207902.fastq.gz	Fastqsanger.gz

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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

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

2019-12-30 | GSE138718 | GEO

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

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

| PRJNA576898 | ENA

Inducible heart specific MPC1 knockdown in adult mice

Project description:We report that knocking down the Mitochondrial Pruvate Carrier 1 (MPC1) in the hearts of adult mice is sufficient to induce hypertrophy and heart failure.

2020-06-09 | GSE152055 | 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

Loss of the mitochondrial pyruvate carrier promotes stem cell gene expression in colon adenomas.

Project description:Loss of the mitochondrial pyruvate carrier promotes stem cell gene expression in AOMDSS colon adenomas, though loss of Apc promotes a more unified pehnotype.

2019-09-02 | GSE136710 | GEO

Mitochondrial carrier homolog 2 (MTCH2) regulates the differentiation of AML cells by controlling pyruvate entry into the mitochondria, nuclear localization of pyruvate dehydrogenase complex and H3 and H4 histone acetylation

Project description:Inhibiting MTCH2 or the Mitochondrial Pyruvate Carrier increased levels of pyruvate and pyruvate dehydrogenase in the nucleus leading to differentiation and loss of stemness in AML.

2020-09-01 | GSE103834 | 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.

2022-04-20 | GSE184718 | 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.

2023-09-01 | GSE221442 | GEO

Mitochondrial pyruvate metabolism regulates the activation of quiescent adult neural stem cells

Project description:Cellular metabolism is important for adult neural stem/progenitor cell (NSPC) behavior. However, its role in the transition from quiescence to proliferation is not fully understood. We here show that the mitochondrial pyruvate carrier (MPC) plays a crucial and unexpected part in this process. MPC transports pyruvate into mitochondria, linking cytosolic glycolysis to mitochondrial tricarboxylic acid cycle and oxidative phosphorylation. Despite its metabolic key function, the role of MPC in NSPCs has not been addressed. We show that quiescent NSPCs have an active mitochondrial metabolism and express high levels of MPC. Pharmacological MPC inhibition increases aspartate and triggers NSPC activation. Furthermore, genetic Mpc1 ablation in vitro and in vivo also activates NSPCs, which differentiate into mature neurons, leading to overall increased hippocampal neurogenesis in adult and aged mice. These findings highlight the importance of metabolism for NSPC regulation and identify an important pathway through which mitochondrial pyruvate import controls NSPC quiescence and activation.

2023-01-26 | GSE220663 | GEO

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