Roberts D J, Miyamoto S
Department of Pharmacology, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA, USA.
Cell Death Differ. 2015 Feb;22(2):248-57. doi: 10.1038/cdd.2014.173. Epub 2014 Oct 17.
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.
越来越多的证据表明，代谢途径和细胞存活途径密切相关，共享共同的信号分子。己糖激酶催化葡萄糖磷酸化，这是糖酵解的限速第一步。己糖激酶II（HK-II）是胰岛素敏感组织如心脏、骨骼肌和脂肪组织中的主要同工型。它在许多与肿瘤细胞中增强的有氧糖酵解（瓦伯格效应）相关的肿瘤类型中也上调。除了在糖酵解中的基本作用外，HK-II越来越被认为是存活信号连接点的一个组成部分。本综述总结了在理解HK-II的保护作用、控制细胞生长、预防线粒体死亡途径和增强自噬方面的最新进展，特别关注HK-II与Akt/mTOR途径之间的相互作用，以将代谢状态与细胞存活控制整合起来。
