ArticleThe Biochemical journal2004
In self-defence: hexokinase promotes voltage-dependent anion channel closure and prevents mitochondria-mediated apoptotic cell death.
Article in The Biochemical journal, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 187 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
187 citing papers in PubMed, 1 synthesis or guideline pooled it, 397 citations in OpenAlex.
- Poor prognosis of hexokinase 2 overexpression in solid tumors of digestive system: a meta-analysis.Oncotarget · 2017Pooled it
- De novo variants in HK1 associated with neurodevelopmental abnormalities and visual impairment.European journal of human genetics : EJHG · 2019Trial
- Anti-kelch-like 12 and anti-hexokinase 1: novel autoantibodies in primary biliary cirrhosis.Liver international : official journal of the International Association for the Study of the Liver · 2015Trial
- Role of voltage-dependent anion channel 1 in neurodegeneration: Mechanisms, implications, and therapeutic potential.Neural regeneration research · 2026Article
- Review
- Hexokinase expansion in thermophilic snails supports extreme heat tolerance.Science China. Life sciences · 2026Article
- Chronic hypoxia protects the mouse heart from oxidative stress via HIF-1α-mitochondria crosstalk.Cellular and molecular life sciences : CMLS · 2026Article
- Targeting VDAC1 to protect against mitochondria-linked cell death pathways: apoptosis, pyroptosis, ferroptosis, and associated diseases.Apoptosis : an international journal on programmed cell death · 2026Article
- Amyloid-β and Mitochondrial Membranes: A Missing Link in Alzheimer's Pathogenesis.Molecular neurobiology · 2026Review
- VDAC2: an emerging pivotal and multifaceted regulator in tumor biology.Apoptosis : an international journal on programmed cell death · 2026Review
- Mitochondria-ER crosstalk via MAMS: Bridging cellular homeostasis and cancer progression.Apoptosis : an international journal on programmed cell death · 2026Review
- Hexokinase 2 is an RNA-binding protein that regulates mRNA translation independently of glycolysis and induces melanoma cell proliferation.PLoS biology · 2025Article
- Is the Voltage-Dependent Anion Channel a Major Player in Neurodegenerative Diseases?International journal of molecular sciences · 2025Review
- Metformin-Induced Apoptosis Is Mediated Through Mitochondrial VDAC1.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Resveratrol's Pro-Apoptotic Effects in Cancer Are Mediated Through the Interaction and Oligomerization of the Mitochondrial VDAC1.International journal of molecular sciences · 2025Article
- VDAC1: A Key Player in the Mitochondrial Landscape of Neurodegeneration.Biomolecules · 2024Review
- Decoding Cancer through Silencing the Mitochondrial Gatekeeper VDAC1.Biomolecules · 2024Review
- VDAC1-Based Peptides as Potential Modulators of VDAC1 Interactions with Its Partners and as a Therapeutic for Cancer, NASH, and Diabetes.Biomolecules · 2024Review
- Targeting the Warburg effect: A revisited perspective from molecular mechanisms to traditional and innovative therapeutic strategies in cancer.Acta pharmaceutica Sinica. B · 2024Review
- Combining nano-differential scanning fluorimetry and microscale thermophoresis to investigate VDAC1 interaction with small molecules.Journal of enzyme inhibition and medicinal chemistry · 2023Article
127 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In tumour cells, elevated levels of mitochondria-bound isoforms of hexokinase (HK-I and HK-II) result in the evasion of apoptosis, thereby allowing the cells to continue proliferating. The molecular mechanisms by which bound HK promotes cell survival are not yet fully understood. Our studies relying on the purified mitochondrial outer membrane protein VDAC (voltage-dependent anion channel), isolated mitochondria or cells in culture suggested that the anti-apoptotic activity of HK-I occurs via modulation of the mitochondrial phase of apoptosis. In the present paper, a direct interaction of HK-I with bilayer-reconstituted purified VDAC, inducing channel closure, is demonstrated for the first time. Moreover, HK-I prevented the Ca(2+)-dependent opening of the mitochondrial PTP (permeability transition pore) and release of the pro-apoptotic protein cytochrome c. The effects of HK-I on VDAC activity and PTP opening were prevented by the HK reaction product glucose 6-phosphate, a metabolic intermediate in most biosynthetic pathways. Furthermore, glucose 6-phosphate re-opened both the VDAC and the PTP closed by HK-I. The HK-I-mediated effects on VDAC and PTP were not observed using either yeast HK or HK-I lacking the N-terminal hydrophobic peptide responsible for binding to mitochondria, or in the presence of an antibody specific for the N-terminus of HK-I. Finally, HK-I overexpression in leukaemia-derived U-937 or vascular smooth muscle cells protected against staurosporine-induced apoptosis, with a decrease of up to 70% in cell death. These results offer insight into the mechanisms by which bound HK promotes tumour cell survival, and suggests that its overexpression not only ensures supplies of energy and phosphometabolites, but also reflects an anti-apoptotic defence mechanism.
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Registered trials
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.