Hexokinase II integrates energy metabolism and cellular protection: Akting on mitochondria and TORCing to autophagy

• Published in: Cell death and differentiation Vol. 22; no. 2; pp. 248 - 257
• Main Authors: Roberts, D J, Miyamoto, S
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 01.02.2015
• Subjects: Animals; Autophagy; Energy Metabolism; Glycolysis; Hexokinase - metabolism; Humans; Mechanistic Target of Rapamycin Complex 1; Mice; Mitochondria - metabolism; Multiprotein Complexes - metabolism; Phosphorylation; Proto-Oncogene Proteins c-akt - metabolism; Review; Signal Transduction; TOR Serine-Threonine Kinases - metabolism
• ISSN: 1350-9047; 1476-5403
• DOI: 10.1038/cdd.2014.173

Accumulating evidence reveals that metabolic and cell survival pathways are closely related, sharing common signaling molecules. Hexokinase catalyzes the phosphorylation of glucose, the rate-limiting first step of glycolysis. Hexokinase II (HK-II) is a predominant isoform in insulin-sensitive tissues such as heart, skeletal muscle, and adipose tissues. It is also upregulated in many types of tumors associated with enhanced aerobic glycolysis in tumor cells, the Warburg effect. In addition to the fundamental role in glycolysis, HK-II is increasingly recognized as a component of a survival signaling nexus. This review summarizes recent advances in understanding the protective role of HK-II, controlling cellular growth, preventing mitochondrial death pathway and enhancing autophagy, with a particular focus on the interaction between HK-II and Akt/mTOR pathway to integrate metabolic status with the control of cell survival.