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Abbreviations 2HG 2-Hydroxyglutarate 5-FU 5-Fluorouracil 5hmC 5-Hydroxymethylcytosine 5mC 5-Methylcytosine ACLY ATP-Citrate Lyase ACOD1 Aconitase Dehydrogenase ALDOA Aldolase A AML Acute Myeloid Leukemia AMPK AMP-Activated Protein Kinase APRT Adenine Phosphoribosyltransferase ATP Adenosine Triphosphate BACH1 BTB Domain and CNC Homolog 1 CCL2 Chemokine (C–C Motif) Ligand 2 CCL7 Chemokine (C–C Motif) Ligand 7 cGAS Cyclic GMP-AMP Synthase CRPC Castration-Resistant Prostate Cancer D-2HG D-2-Hydroxyglutarate L-2HG L-2-Hydroxyglutarate DCK Deoxycytidine Kinase DCs Dendritic Cells DDX1 DEAD-Box Helicase 1 DDX21 DEAD-Box Helicase 21 DHF Dihydrofolate DHFR Dihydrofolate Reductase DHODH Dihydroorotate Dehydrogenase DHX36 DEAH-Box Helicase 36 DNA Deoxyribonucleic Acid dNTP Deoxynucleotide Triphosphate EGLN HIF prolyl 4-hydroxylases ENO1 α-Enolase 1 ER Endoplasmic Reticulum ERK Extracellular Signal-Regulated Kinas FBP Fructose-1,6-Bisphosphate FH Fumarate Hydratase G6P Glucose-6-Phosphate G6PD Glucose-6-Phosphate Dehydrogenase GEF Guanine Nucleotide Exchange Factor GLUT1 Glucose Transporter 1 GLUT3 Glucose Transporter 3 GRHL3 Grainyhead-Like Transcription Factor 3 GSK3 Glycogen Synthase Kinase 3 HATs Histone Acetyltransferases HDACs Histone Deacetylases HGPRT Hypoxanthine–Guanine Phosphoribosyltransferase HIF-1α Hypoxia-Inducible Factor-1α HK2 Hexokinase 2 HKDC1 Hexokinase Domain-Containing 1 HR Homologous Recombination ICB Immune Checkpoint Blockade IDH1 Isocitrate Dehydrogenase 1 IDH2 Isocitrate Dehydrogenase 2 IFN-β Interferon-β IMPA1 Inositol Monophosphatase 1 IMPDH2 Inosine Monophosphate Dehydrogenase 2 IPs Inositol Phosphates IRF6 Interferon Regulatory Factor 6 IRG1 Immune-Responsive Gene 1 ISYNA1 Inositol-3-Phosphate Synthase 1 JHDM1A JmjC Domain-Containing Histone Demethylase 1A KDM2A Lysine Demethylase 2A KDM4A Lysine Demethylase 4A KEAP1 Kelch-Like ECH-Associated Protein 1 L-2HG L-2-Hydroxyglutarate L2HGDH L-2HG Dehydrogenase LDH Lactate Dehydrogenase LDHA Lactate Dehydrogenase A LDHB Lactate Dehydrogenase B MAVS Mitochondrial Antiviral-Signaling Protein MCTs Monocarboxylate Transporters MDH Malate Dehydrogenase ME1 Malic Enzyme 1 5,10-CH2-THF 5,10-Methylenetetrahydrofolate MRN MRE11–RAD50–NBS1 mTOR Mammalian Target of Rapamycin MTHFD1 Methylene Tetrahydrofolate Dehydrogenase 1 MTHFD2 Methylene Tetrahydrofolate Dehydrogenase 2 MTX Methotrexate NAD + Nicotinamide Adenine Dinucleotide (Oxidized) NADH Nicotinamide Adenine Dinucleotide (Reduced) NADPH Nicotinamide Adenine Dinucleotide Phosphate (Reduced) NBS1 Nibrin NFAT Nuclear Factor of Activated T-Cells NK Natural Killer NMPs Nucleoside Monophosphates NSCLC Non-Small Cell Lung Cancer NSUN2 RNA 5-Methylcytosine Methyltransferase OXPHOS Oxidative Phosphorylation PARPs Poly(ADP-Ribose) Polymerases PC Pyruvate Carboxylase PCSCs Prostate Cancer Stem Cells PD-1 Programmed Cell Death Protein 1 PDH Pyruvate dehydrogenase PDXs Patient-Derived Xenografts PDH Pyruvate Dehydrogenase PD-L1 Programmed Death-Ligand 1 PEP Phosphoenolpyruvate PFK1 Phosphofructokinase-1 PHB2 Prohibitin 2 PI Phosphatidylinositol PIPs Phosphatidylinositol Phosphates PKM2 Pyruvate Kinase M2 PNP Purine Nucleoside Phosphorylase PPP Pentose Phosphate Pathway PRPP Phosphoribosyl Pyrophosphate PROTACs Proteolysis-Targeting Chimeras R5P Ribose-5-Phosphate RIG-I Retinoic Acid-Inducible Gene I RLR RIG-I-Like Receptor RNR Ribonucleotide Reductase ROS Reactive Oxygen Species RTKs Receptor Tyrosine Kinases SAM S-adenosyl-L-methionine SDH Succinate Dehydrogenase SERCA Sarco/ER Ca2 + -ATPase SHMT Serine Hydroxymethyltransferase SLC13A3 Solute Carrier Family 13 Member 3 SLC25A1 Solute Carrier Family 25 Member 1 SLC5A3 Sodium/Myo-Inositol Cotransporter STAT1 Signal Transducer and Activator of Transcription 1 STING Stimulator of Interferon Genes TALDO Transaldolase TCA Tricarboxylic Acid TET Ten-Eleven Translocation TGF-β Transforming Growth Factor-β THF Tetrahydrofolate TK1/2 Thymidine Kinase ½ TKT Transketolase TME Tumor Microenvironment TNF-α Tumor Necrosis Factor-α TRAMP Transgenic Adenocarcinoma of the Mouse Prostate Tregs Regulatory T Cells TRIF TIR-Domain-Containing Adapter-Inducing Interferon-β TS Thymidylate Synthase UCK1/2 Uridine-Cytidine Kinase 1/2 UDP-GlcNAc Uridine Diphosphate N-Acetylglucosamine UMP Uridine Monophosphate VEGF Vascular Endothelial Growth Factor YAP1 Yes-Associated Protein 1 Author contributions H.K.L., B.S.P., and C.C.H

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Lysosomal quality control of cell fate: a novel therapeutic target for human diseases