Glutamine reliance in cell metabolism

Experimental & Molecular Medicine, Journal Year: 2020, Volume and Issue: 52(9), P. 1496 - 1516

Published: Sept. 1, 2020

Abstract As knowledge of cell metabolism has advanced, glutamine been considered an important amino acid that supplies carbon and nitrogen to fuel biosynthesis. A recent study provided a new perspective on mitochondrial metabolism, offering mechanistic insights into metabolic adaptation during tumor hypoxia, the emergence drug resistance, glutaminolysis-induced reprogramming presenting strategies target in cancer cells. In this review, we introduce various biosynthetic bioenergetic roles based compartmentalization explain why cells exhibit reliance glutamine. Additionally, examined whether derivatives contribute epigenetic regulation associated with tumorigenesis. addition, discussing transporters, propose for therapeutic intervention cancer.

Language: Английский

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Redox regulation of immunometabolism

Nature reviews. Immunology, Journal Year: 2020, Volume and Issue: 21(6), P. 363 - 381

Published: Dec. 18, 2020

Language: Английский

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Changes in Glutathione Content in Liver Diseases: An Update

Antioxidants, Journal Year: 2021, Volume and Issue: 10(3), P. 364 - 364

Published: Feb. 28, 2021

Glutathione (GSH), a tripeptide particularly concentrated in the liver, is most important thiol reducing agent involved modulation of redox processes. It has also been demonstrated that GSH cannot be considered only as mere free radical scavenger but it takes part network governing choice between survival, necrosis and apoptosis well altering function signal transduction transcription factor molecules. The purpose present review to provide an overview on molecular biology system; therefore, synthesis, metabolism regulation will reviewed. multiple functions described, importance compartmentalization into distinct subcellular pools inter-organ transfer. Furthermore, we highlight close relationship existing content pathogenesis liver disease, such non-alcoholic fatty disease (NAFLD), alcoholic (ALD), chronic cholestatic injury, ischemia/reperfusion damage, hepatitis C virus (HCV), B (HBV) hepatocellular carcinoma. Finally, potential therapeutic benefits GSH-related medications, described for each disorder taken account.

Language: Английский

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Tumour metabolism and its unique properties in prostate adenocarcinoma

Nature Reviews Urology, Journal Year: 2020, Volume and Issue: 17(4), P. 214 - 231

Published: Feb. 28, 2020

Language: Английский

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The Multifaceted Pyruvate Metabolism: Role of the Mitochondrial Pyruvate Carrier

Biomolecules, Journal Year: 2020, Volume and Issue: 10(7), P. 1068 - 1068

Published: July 17, 2020

Pyruvate, the end product of glycolysis, plays a major role in cell metabolism. Produced cytosol, it is oxidized mitochondria where fuels citric acid cycle and boosts oxidative phosphorylation. Its sole entry point into through recently identified mitochondrial pyruvate carrier (MPC). In this review, we report latest findings on physiology MPC discuss how dysfunctional can lead to diverse pathologies, including neurodegenerative diseases, metabolic disorders, cancer.

Language: Английский

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Glutathione Metabolism and the Novel Role of Mitochondrial GSH in Retinal Degeneration

Antioxidants, Journal Year: 2021, Volume and Issue: 10(5), P. 661 - 661

Published: April 24, 2021

Glutathione (GSH) is present ubiquitously, and its role as a crucial cellular antioxidant in tissues, including the retina, well established. GSH’s function arises from ability to scavenge reactive oxygen species or serve an essential cofactor for GSH S-transferases peroxidases. This review summarizes general functions, retinal distribution, disorders linked deficiency, emerging mitochondrial (mGSH) function. Though synthesized only cytosol, presence of multiple cell organelles suggests requirement active transport across organellar membranes. The localization distribution 2-oxoglutarate carrier (OGC) dicarboxylate (DIC), two recently characterized proteins RPE show that these transporters are highly expressed human pigment epithelium (RPE) cells layers, their expression increases with polarity cultured cells. Depletion mGSH levels via inhibition resulted reduced bioenergetic parameters (basal respiration, ATP production, maximal spare respiratory capacity) increased death. These results begin reveal critical maintaining bioenergetics health. Thus, augmentation pool under GSH-deficient conditions may be valuable tool treating disorders, such age-related macular degeneration optic neuropathies, whose pathologies have been associated dysfunction.

Language: Английский

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Mitochondrial pyruvate carrier 1 regulates ferroptosis in drug-tolerant persister head and neck cancer cells via epithelial-mesenchymal transition

Cancer Letters, Journal Year: 2021, Volume and Issue: 507, P. 40 - 54

Published: March 18, 2021

Language: Английский

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Advancing Cancer Treatment by Targeting Glutamine Metabolism—A Roadmap

Cancers, Journal Year: 2022, Volume and Issue: 14(3), P. 553 - 553

Published: Jan. 22, 2022

Tumor growth and metastasis strongly depend on adapted cell metabolism. Cancer cells adjust their metabolic program to specific energy needs in response an often challenging tumor microenvironment. Glutamine metabolism is one of the pathways that can be successfully targeted cancer treatment. The dependence many hematological solid tumors glutamine associated with mitochondrial glutaminase (GLS) activity enables channeling into tricarboxylic acid (TCA) cycle, generation ATP NADPH, regulation glutathione homeostasis reactive oxygen species (ROS). Small molecules target through inhibition GLS therefore simultaneously limit availability increase oxidative stress. However, some cancers reprogram evade this trap. Therefore, effectiveness treatment strategies rely solely limited. In review, we discuss molecular are linked dysregulated multiple types. We further summarize review current clinical trials glutaminolysis patients. Finally, put perspective deploy a combined targeting along other or potential for applications.

Language: Английский

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The mitochondrial pyruvate carrier (MPC) complex mediates one of three pyruvate-supplying pathways that sustain Arabidopsis respiratory metabolism

The Plant Cell, Journal Year: 2021, Volume and Issue: 33(8), P. 2776 - 2793

Published: May 25, 2021

Malate oxidation by plant mitochondria enables the generation of both oxaloacetate and pyruvate for tricarboxylic acid (TCA) cycle function, potentially eliminating need transport into in plants. Here, we show that absence mitochondrial carrier 1 (MPC1) causes co-commitment loss its putative orthologs, MPC3/MPC4, eliminates Arabidopsis thaliana mitochondria, proving it is essential MPC complex function. While either or pyruvate-generating NAD-malic enzyme (NAD-ME) did not cause vegetative phenotypes, lack reduced growth caused an increase cellular levels, indicating a block respiratory metabolism, elevated levels branched-chain amino acids at night, sign alterative substrate provision respiration. 13C-pyruvate feeding leaves lacking showed metabolic homeostasis was largely maintained except alanine glutamate, transamination contributes to restoration network operating equilibrium delivering independently matrix. Inhibition aminotransferases when MPC1 absent resulted extremely retarded phenotypes Arabidopsis, suggesting all pyruvate-supplying enzymes work synergistically support TCA sustained growth.

Language: Английский

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The Importance of Mitochondrial Pyruvate Carrier in Cancer Cell Metabolism and Tumorigenesis

Cancers, Journal Year: 2021, Volume and Issue: 13(7), P. 1488 - 1488

Published: March 24, 2021

Pyruvate is a key molecule in the metabolic fate of mammalian cells; it crossroads from where metabolism proceeds either oxidatively or ends with production lactic acid. regulated by many enzymes that together control carbon flux. Mitochondrial pyruvate carrier (MPC) responsible for importing cytosol to mitochondrial matrix, phosphorylated produce adenosine triphosphate (ATP) and generate intermediates used multiple biosynthetic pathways. MPC activity has an important role glucose homeostasis, its alteration associated diabetes, heart failure, neurodegeneration. In cancer, however, controversy surrounds function. some cancers, upregulation appears be poor prognosis. However, most transformed cells undergo switch oxidative glycolytic metabolism, so-called Warburg effect, which, amongst other possibilities, induced malfunction downregulation. Consequently, impaired function might induce tumors strong proliferative, migratory, invasive capabilities. Moreover, cancer secrete lactate, acidifying microenvironment, which turn induces angiogenesis, immunosuppression, expansion stromal cell populations supporting tumor growth. This review examines latest findings regarding tumorigenic processes affected MPC.

Language: Английский

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