Glycogen synthase kinase-3 (GSK3) controls deoxyglucose-induced mitochondrial biogenesis in human neuroblastoma SH-SY5Y cells

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-GSK3 beta promoted whereas GSK3 beta-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 mitochondria! transcription. Together, our results show that GSK3 regulates mitochondrial biogenesis induced by glycolysis inhibition. (C) 2013 Elsevier B.V. and Mitochondria Research Society. All rights reserved.