ArticleProceedings of the National Academy of Sciences of the United States of America2012
Mitochondrial hexokinase II (HKII) and phosphoprotein enriched in astrocytes (PEA15) form a molecular switch governing cellular fate depending on the metabolic state.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers, 1 of them a synthesis that pooled it.
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Who cites it
47 citing papers in PubMed, 1 synthesis or guideline pooled it, 74 citations in OpenAlex.
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- Measuring cerebral glucose metabolism by chemical exchange-sensitive spin-lock (CESL) MRI of 2-deoxy-D-glucose in rodents.PloS one · 2026Article
- Evaluating the Diagnostic Value and Molecular Mechanism of Energy Metabolism-Related Gene PEA15 in Sepsis.Journal of inflammation research · 2026Article
- Neural Metabolic Networks: Key Elements of Healthy Brain Function.Journal of neurochemistry · 2025Review
- Reinventing the Penumbra - the Emerging Clockwork of a Multi-modal Mechanistic Paradigm.Translational stroke research · 2023Review
- Venlafaxine's effect on resilience to stress is associated with a shift in the balance between glucose and fatty acid utilization.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2023Article
- How Do Hexokinases Inhibit Receptor-Mediated Apoptosis?Biology · 2022Review
- Human Cerebral Perfusion, Oxygen Consumption, and Lactate Production in Response to Hypoxic Exposure.Cerebral cortex (New York, N.Y. : 1991) · 2022Article
- Metabolic regulation of T cell development.Frontiers in immunology · 2022Review
- Differential Effects of 2-Deoxyglucose and Glucose Deprivation on 4-Hydroxynonenal Dependent Mitochondrial Dysfunction in Primary Neurons.Frontiers in aging · 2022Article
- Loss of hexokinase 1 sensitizes ovarian cancer to high-dose metformin.Cancer & metabolism · 2021Article
- Novel Anti-inflammatory Effects of Canagliflozin Involving Hexokinase II in Lipopolysaccharide-Stimulated Human Coronary Artery Endothelial Cells.Cardiovascular drugs and therapy · 2021Article
- Wdfy3 regulates glycophagy, mitophagy, and synaptic plasticity.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2021Article
- Hexokinases inhibit death receptor-dependent apoptosis on the mitochondria.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Rapid 3D phenotypic analysis of neurons and organoids using data-driven cell segmentation-free machine learning.PLoS computational biology · 2021Article
- BMP4 Moderates Glycolysis and Regulates Activation and Interferon-Gamma Production in CD4+ T Cells.Frontiers in immunology · 2021Article
- Upregulated proteoglycan-related signaling pathways in fluid flow shear stress-treated podocytes.American journal of physiology. Renal physiology · 2020Article
- The carboxyl-terminal sequence of bim enables bax activation and killing of unprimed cells.eLife · 2020Article
Corrections and comments
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Authors and funding
16 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The metabolic state of a cell is a key determinant in the decision to live and proliferate or to die. Consequently, balanced energy metabolism and the regulation of apoptosis are critical for the development and maintenance of differentiated organisms. Hypoxia occurs physiologically during development or exercise and pathologically in vascular disease, tumorigenesis, and inflammation, interfering with homeostatic metabolism. Here, we show that the hypoxia-inducible factor (HIF)-1-regulated glycolytic enzyme hexokinase II (HKII) acts as a molecular switch that determines cellular fate by regulating both cytoprotection and induction of apoptosis based on the metabolic state. We provide evidence for a direct molecular interactor of HKII and show that, together with phosphoprotein enriched in astrocytes (PEA15), HKII inhibits apoptosis after hypoxia. In contrast, HKII accelerates apoptosis in the absence of PEA15 and under glucose deprivation. HKII both protects cells from death during hypoxia and functions as a sensor of glucose availability during normoxia, inducing apoptosis in response to glucose depletion. Thus, HKII-mediated apoptosis may represent an evolutionarily conserved altruistic mechanism to eliminate cells during metabolic stress to the advantage of a multicellular organism.
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