Glucose Phosphorylation and Mitochondrial Binding Are Required for the Protective Effects of Hexokinases I and II

Sun, Lin; Shukair, Shetha; Naik, Tejaswitha J; Moazed, Farzad; Ardehali, Hossein

doi:10.1128/mcb.00224-07

Cited by 222 publications

(248 citation statements)

References 57 publications

Supporting

Mentioning

226

Contrasting

Order By: Relevance

“…85 Thus the protective effect of HK-II could be due to its cytosolic activity to increase NADPH levels through the pentose phosphate pathway producing antioxidant effects. 80 This hypothesis is supported by a recent paper using cardiac-specific HK-II transgenic (TG) mice. 82 Cardiac hypertrophy induced by isoproterenol infusion is attenuated in the TG mice and this is accompanied by reduced reactive oxygen species (ROS) levels in cardiomyocytes overexpressing HK-II.…”

Section: Pro-survival Effect Of Hk-iimentioning

confidence: 82%

“…[75][76][77][78][79][80][81][82] Conversely, decreased HK-II levels sensitize cells to apoptotic or necrotic stimuli. Overexpression of HK-II confers cellular protection against H 2 O 2 in cardiomyocytes 79,80,82 and also prevents maladaptive hypertrophy in vivo heart. 82 Heterozygotic HK-II knockout hearts are more susceptible to ischemia/reperfusion injury as well as pressure overload.…”

Section: Pro-survival Effect Of Hk-iimentioning

confidence: 99%

“…We and others have also reported that an increase in mitoHK-II has an inhibitory effect on Ca 2+ -and ROS-induced mPTP opening and that a large dissociation of mitoHK-II sensitizes mPTP opening and cell death. 77,80,82,83,[96][97][98] A series of studies have demonstrated that mitoHK-II has an ability to decrease ROS generation at mitochondria to prevent opening of the mPTP. 77,80,82,84,99 As mentioned earlier, mitoHK ensures tight coupling of glucose phosphorylation and mitochondrial ATP generation.…”

Section: Pro-survival Effect Of Hk-iimentioning

confidence: 99%

“…Akt mediated increases in HK-II expression and mitochondrial association support the growth response through efficient energy production 4,17,18 as well as preserving mitochondrial integrity. 3,15,28,76,77,79,80,93,96,97,118,178 In contrast, regulation of the pentose phosphate pathway or glycogenesis by HKs is considered as a cytosolic event. Thus Akt-mediated phosphorylation endows HK-II with diverse and complex roles to regulate energy production versus storage, and cell growth and survival by changing its intracellular localization.…”

Section: Overall Summary Of Interaction Between Hk-ii and Akt/ Torc1mentioning

confidence: 99%

See 3 more Smart Citations

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

2014

View full text Add to dashboard Cite

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.

show abstract

Section: Pro-survival Effect Of Hk-iimentioning

confidence: 82%

Section: Pro-survival Effect Of Hk-iimentioning

confidence: 99%

Section: Pro-survival Effect Of Hk-iimentioning

confidence: 99%

Section: Overall Summary Of Interaction Between Hk-ii and Akt/ Torc1mentioning

confidence: 99%

See 2 more Smart Citations

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

2014

View full text Add to dashboard Cite

show abstract

“…Interestingly, overexpressing HK I and II can also induce the protein kinase C isoform e (PKCe)-catalyzed phosphorylation of VDAC (Sun et al, 2008), which inhibits PTPC opening (Baines et al, 2003). Catalytically inactive HK mutants fail to confer protection against MOMP (Sun et al, 2008), suggesting that the enzymatic activity of HK somehow contributes to MOMP inhibition.…”

mentioning

confidence: 99%

Disruption of the hexokinase–VDAC complex for tumor therapy

2008

View full text Add to dashboard Cite

Endothelial Metabolic Control of Lymphangiogenesis

Lee

et al. 2018

BioEssays

View full text Add to dashboard Cite

Lymphangiogenesis is an important developmental process that is critical to regulation of fluid homeostasis, immune surveillance and response as well as pathogenesis of a number of diseases, among them cancer, inflammation, and heart failure. Specification, formation, and maturation of lymphatic blood vessels involves an interplay between a series of events orchestrated by various transcription factors that determine expression of key genes involved in lymphangiogenesis. These are traditionally thought to be under control of several key growth factors including vascular growth factor-C (VEGF-C) and fibroblast growth factors (FGFs). Recent insights into VEGF and FGF signaling point to their role in control of endothelial metabolic processes such as glycolysis and fatty acid oxidation that, in turn, play a major role in regulation of lymphangiogenesis. These advances have significantly increased our understanding of lymphatic biology and opened new therapeutic vistas. Here we review our current understanding of metabolic controls in the lymphatic vasculature.

show abstract

Glucose Phosphorylation and Mitochondrial Binding Are Required for the Protective Effects of Hexokinases I and II

Cited by 222 publications

References 57 publications

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

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

Disruption of the hexokinase–VDAC complex for tumor therapy

Endothelial Metabolic Control of Lymphangiogenesis

Contact Info

Product

Resources

About