ArticleKidney international2011
Hexokinase regulates Bax-mediated mitochondrial membrane injury following ischemic stress.
Article in Kidney international, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 78 citations in OpenAlex.
- Deciphering Bax Dynamics: Regulation, Retrotranslocation, and Mitochondrial Interplay in the Commitment to Apoptosis: A Narrative Review.Health science reports · 2026Article
- SGLT2 inhibitor empagliflozin ameliorates tubulointerstitial fibrosis in DKD by downregulating renal tubular PKM2.Cellular and molecular life sciences : CMLS · 2025Article
- Glycolysis in hepatic stellate cells coordinates fibrogenic extracellular vesicle release spatially to amplify liver fibrosis.Science advances · 2024Article
- Review
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- HK2: a potential regulator of osteoarthritis via glycolytic and non-glycolytic pathways.Cell communication and signaling : CCS · 2022Review
- Reticulon-1A mediates diabetic kidney disease progression through endoplasmic reticulum-mitochondrial contacts in tubular epithelial cells.Kidney international · 2022Article
- Insulin, Muscle Glucose Uptake, and Hexokinase: Revisiting the Road Not Taken.Physiology (Bethesda, Md.) · 2022Review
- How Do Hexokinases Inhibit Receptor-Mediated Apoptosis?Biology · 2022Review
- Novel mutation in hexokinase 2 confers resistance to 2-deoxyglucose by altering protein dynamics.PLoS computational biology · 2022Article
- Mechanisms of nucleophosmin (NPM)-mediated regulated cell death elucidated by Hsp70 during renal ischemia.Apoptosis : an international journal on programmed cell death · 2022Article
- Hypothermia Prevents Cardiac Dysfunction during Acute Ischemia Reperfusion by Maintaining Mitochondrial Bioenergetics and by Promoting Hexokinase II Binding to Mitochondria.Oxidative medicine and cellular longevity · 2022Article
- Fructose in the kidney: from physiology to pathology.Kidney research and clinical practice · 2021Article
- MicroRNA‑93 inhibits the apoptosis and inflammatory response of tubular epithelial cells via the PTEN/AKT/mTOR pathway in acute kidney injury.Molecular medicine reports · 2021Article
- Natural product triptolide induces GSDME-mediated pyroptosis in head and neck cancer through suppressing mitochondrial hexokinase-ΙΙ.Journal of experimental & clinical cancer research : CR · 2021Article
- Glucose Metabolism in Acute Kidney Injury and Kidney Repair.Frontiers in medicine · 2021Review
- The Synthetic Flavonoid Derivative GL-V9 Induces Apoptosis and Autophagy in Cutaneous Squamous Cell Carcinoma via Suppressing AKT-Regulated HK2 and mTOR Signals.Molecules (Basel, Switzerland) · 2020Article
- Hexokinase 2 is dispensable for photoreceptor development but is required for survival during aging and outer retinal stress.Cell death & disease · 2020Article
- Inhibition of GSK3β and RIP1K Attenuates Glial Scar Formation Induced by Ischemic StrokeFrontiers in pharmacology · 2020Article
- The inhibition of Bax activation-induced apoptosis by RasGRP2 via R-Ras-PI3K-Akt signaling pathway in the endothelial cells.Scientific reports · 2019Article
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9 authors at 3 institutions in 1 country.
Funding
Abstract
Hexokinase (HK), the rate-limiting enzyme in glycolysis, controls cell survival by promoting metabolism and/or inhibiting apoptosis. Since HK isoforms I and II have mitochondrial targeting sequences, we attempted to separate the protective effects of HK on cell metabolism from those on apoptosis. We exposed renal epithelial cells to metabolic stress causing ATP depletion in the absence of glucose and found that this activated glycogen synthase kinase 3β (GSK3β) and Bax caused mitochondrial membrane injury and apoptosis. ATP depletion led to a progressive HK II dissociation from mitochondria, released mitochondrial apoptosis inducing factor and cytochrome c into the cytosol, activated caspase-3, and reduced cell survival. Compared with control, adenoviral-mediated HK I or II overexpression improved cell survival following stress, but did not prevent GSK3β or Bax activation, improve ATP content, or reduce mitochondrial fragmentation. HK I or HK II overexpression increased mitochondria-associated isoform-specific HK content, and decreased mitochondrial membrane injury and apoptosis after stress. In vivo, HK II localized exclusively to the proximal tubule. Ischemia reduced total renal HK II content and dissociated HK II from proximal tubule mitochondria. In cells overexpressing HK II, Bax and HK II did not interact before or after stress. While the mechanism by which HK antagonizes Bax-mediated apoptosis is unresolved by these studies, one possible scenario is that the two proteins compete for a common binding site on the outer mitochondrial membrane.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.