title: Glycogen synthase kinase-3 (GSK3) controls deoxyglucose-induced mitochondrial biogenesis in human neuroblastoma SH-SY5Y cells.
abstract: Mitochondrial biogenesis, a mitochondrial growth and division process, is crucial for adaptation to metabolic stress. The present study demonstrated that treatment with a specific inhibitor of GSK3, SB216763, attenuated induction of mitochondrial biogenesis by a glycolysis inhibitor, 2-deoxyglucose (2-DG), without affecting this biogenesis at basal condition. Additionally, overexpression of WT-GSK3β promoted whereas GSK3β-KD attenuated 2-DG-induced mitochondrial protein expression. The mitochondrial biogenesis attenuation by GSK3 inhibitor was not due to inhibition of protein degradation. Furthermore, GSK3 inhibition further reduced transcription of mitochondrial (COXII), but not nuclear (VDAC) gene by 2-DG suggesting its participation in 2-DG-induced mitochondrial transcription. Together, our results show that GSK3 regulates mitochondrial biogenesis induced by glycolysis inhibition.
authors: Laboratory of Pharmacology, Chulabhorn Research Institute, 54 KamphaengPhet6 Rd, Bangkok, 10210, Thailand; Chulabhorn Graduate Institute, 54 KamphaengPhet6 Rd, Bangkok 10210, Thailand.
authors: Pronrumpa
authors: P
authors: Ngamsiri
authors: Laboratory of Pharmacology, Chulabhorn Research Institute, 54 KamphaengPhet6 Rd, Bangkok, 10210, Thailand; Chulabhorn Graduate Institute, 54 KamphaengPhet6 Rd, Bangkok 10210, Thailand; Center of Excellence on Environmental Health and Toxicology (EHT), Office of the Higher Education Commission, Thailand. Electronic address: Piyajit@cri.or.th.
authors: Piyajit
authors: P
authors: Watcharasit
authors: Laboratory of Pharmacology, Chulabhorn Research Institute, 54 KamphaengPhet6 Rd, Bangkok, 10210, Thailand; Chulabhorn Graduate Institute, 54 KamphaengPhet6 Rd, Bangkok 10210, Thailand; Center of Excellence on Environmental Health and Toxicology (EHT), Office of the Higher Education Commission, Thailand.
authors: Jutamaad
authors: J
authors: Satayavivad
mesh_terms: D045744:Cell Line, Tumor; D003847:Deoxyglucose / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000378:metabolism; D015870:Gene Expression; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism*; D006801:Humans; D007211:Indoles / Q000378:metabolism; D008301:Maleimides / Q000378:metabolism; D063269:Mitochondrial Turnover; D009474:Neurons / Q000201:enzymology* / Q000378:metabolism / Q000502:physiology*
chemical_list: D004791:Enzyme Inhibitors; D007211:Indoles; D008301:Maleimides; C417521:SB 216763; D003847:Deoxyglucose; D038362:Glycogen Synthase Kinase 3
keywords: 2-DG; 2-Deoxyglucose; AMP-activated protein kinase; AMPK; GAPDH; GSK3; GSK3β-KD; Glyceraldehyde-3-phosphate dehydrogenase; Glycogen synthase kinase-3; Glycogen synthase kinase-3 (α/β); Glycogen synthase kinase-3β-kinase dead; Mitochondrial biogenesis; Mitochondrial cytochrome b; Mitochondrial cytochrome c oxidase subunit II; Mitochondrial cytochrome c oxidase subunit III; Mitochondrial transcription factor A; NRF-1; Nuclear respiratory factor 1; PGC-1α; Peroxisome proliferator-activated receptor gamma coactivator 1α; TFAM; TK2; Thymidine kinase 2; VDAC; Voltage-dependent anion-selective channel; WT-GSK3β; Wild-type-glycogen synthase kinase-3β; mtCOXII; mtCOXIII; mtCYTB