The Key Roles of GSK-3β in Regulating Mitochondrial Activity

• Published in: Cellular physiology and biochemistry Vol. 44; no. 4; pp. 1445 - 1459
• Main Authors: Yang, Kai, Chen, Zhixi, Gao, Juanjuan, Shi, Weimei, Li, Linfu, Jiang, Shan, Hu, Haibo, Liu, Zhiping, Xu, Daohua, Wu, Longhuo
• Format: Journal Article
• Language: English
• Published: Basel, Switzerland S. Karger AG 01.12.2017; Cell Physiol Biochem Press GmbH & Co KG
• Subjects: Alzheimer Disease - drug therapy; Alzheimer's disease; Animals; Apoptosis; Apoptosis - drug effects; Biological Products - pharmacology; Biological Products - therapeutic use; Biosynthesis; Cardiomyocytes; Deoxyribonucleic acid; Diabetes; DNA; Glycogen Synthase Kinase 3 beta - antagonists & inhibitors; Glycogen Synthase Kinase 3 beta - chemistry; Glycogen Synthase Kinase 3 beta - metabolism; Gsk-3β; Insulin resistance; Ischemia; Kinases; Lithium Chloride - pharmacology; Lithium Chloride - therapeutic use; Membrane Potential, Mitochondrial - drug effects; Metabolism; Mitochondria; Mitochondria - drug effects; Mitochondria - metabolism; Mitochondrial apoptosis; Mitochondrial bioenergetics; Mitochondrial biogenesis; Mitochondrial DNA; Mitochondrial motility; Mitochondrial permeability; Mitochondrial Proteins - metabolism; Parkinson's disease; Permeability; Phosphorylation; Proteins; Review; Rodents; Gsk-3β; Mitochondrial apoptosis; Mitochondrial biogenesis; Mitochondrial bioenergetics; Mitochondrial motility; Mitochondrial permeability
• ISSN: 1015-8987; 1421-9778; 1421-9778
• DOI: 10.1159/000485580

Glycogen synthase kinase-3β (GSK-3β), a serine/threonine protein kinase, has been reported to show essential roles in molecular pathophysiology of many diseases. Mitochondrion is a dynamic organelle for producing cellular energy and determining cell fates. Stress-induced translocated GSK-3β may interact with mitochondrial proteins, including PI3K-Akt, PGC-1α, HK II, PKCε, components of respiratory chain, and subunits of mPTP. Mitochondrial pool of GSK-3β has been implicated in mediation of mitochondrial functions. GSK-3β exhibits the regulatory effects on mitochondrial biogenesis, mitochondrial bioenergetics, mitochondrial permeability, mitochondrial motility, and mitochondrial apoptosis. The versatile functions of GSK-3β might be associated with its wide range of substrates. Accumulative evidence demonstrates that GSK-3β inactivation may be potentially developed as the promising strategy in management of many diseases, such as Alzheimer’s disease (AD) and Parkinson’s disease (PD). Intensive efforts have been made for exploring GSK-3β inhibitors. Natural products provide us a great source for screening new lead compounds in inactivation of GSK-3β. The key roles of GSK-3β in mediation of mitochondrial functions are discussed in this review.