ArticleCell research2017
Mitochondrial PKM2 regulates oxidative stress-induced apoptosis by stabilizing Bcl2.
Article in Cell research, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 198 papers, 1 of them a synthesis that pooled it.
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Who cites it
198 citing papers in PubMed, 1 synthesis or guideline pooled it, 341 citations in OpenAlex.
- Interplay Between Glucose Metabolism and Chromatin Modifications in Cancer.Frontiers in cell and developmental biology · 2021Pooled it
- Mitochondrial Metabolic Reprogramming in Glioma: Mechanisms of Tumorigenesis and Implications for Clinical Therapy.CNS neuroscience & therapeutics · 2026Review
- Mechanistic Insights intoInternational journal of molecular sciences · 2026Article
- Oxidative Phosphorylation and Fatty Acid Oxidation Are Central to Mitochondrial Metabolism Rewiring in CML Stem/Progenitor Cell Survival.Pathophysiology : the official journal of the International Society for Pathophysiology · 2026Review
- PKM2 Inhibitors Induce Autophagic Cell Death Through Suppression of PKM2-Mediated Glycolysis in Cisplatin-Resistant Ovarian Cancer Cells.International journal of molecular sciences · 2026Article
- Compression-induced metabolic adaptation drives confined tumor cell migration and distant metastasis via malate-dependent microtubule reinforcement.Cell research · 2026Article
- Exploring the role of protein homeostasis regulation in glycolysis in head and neck tumors.Human cell · 2026Review
- Mitochondria-transliterated ALDH1L1 functions as a feedback regulator of redox homeostasis in cancer cells to enhance the resistance to pro-oxidative therapy.Cell death and differentiation · 2026Article
- Qianyang Yuyin granule modulates glycolysis and inflammatory response to treat hypertensive cardiac remodeling.Journal of traditional Chinese medicine = Chung i tsa chih ying wen pan · 2026Article
- Quantitative Phosphoproteomics Identifies Myofibrillar Protein Phosphorylation Mediated by Pyruvate Kinase M2 in Beef.Foods (Basel, Switzerland) · 2026Article
- Dimeric PKM2 in chondrocytes impairs mitochondrial homeostasis in osteoarthritis.Cell death & disease · 2026Article
- Review
- The moonlighting functions of glycolytic enzymes in tumorigenesis.Cellular oncology (Dordrecht, Netherlands) · 2026Review
- Does CD30 loss preclude the diagnosis of anaplastic lymphoma kinase-positive anaplastic large cell lymphoma? Insights from a rare case.CytoJournal · 2026Article
- Notoginsenoside R1 modulates the ATF4-CHOP-Bcl2 signaling pathway to alleviate mitochondrial stress damage and apoptosis in asthmatic airway epithelial cells.Frontiers in immunology · 2026Article
- Unraveling the synergy of inflammation and apoptosis in sepsis-induced acute lung injury: Insights and therapeutic perspectives (Review).Molecular medicine reports · 2026Review
- BAK and BAX: Therapeutic Targets for Acute Myocardial Infarction and Myocardial Ischemia-Reperfusion Injury.Biology · 2025Review
- Compression-induced NF-κB activation sustains tumor cell survival in confinement by detoxifying aldehydes and promotes metastasis.Nature communications · 2025Article
- Ergosterol-loaded brain-targeted liposomes attenuate stroke via gut microbiota-metabolite-brain axis modulation.Journal of nanobiotechnology · 2025Article
- Metabolic enzyme-associated protein-protein interactions (mPPIs) in cancer: potential vulnerability for cancer treatment?Acta pharmacologica Sinica · 2025Review
138 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
13 authors at 6 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Pyruvate kinase M2 isoform (PKM2) catalyzes the last step of glycolysis and plays an important role in tumor cell proliferation. Recent studies have reported that PKM2 also regulates apoptosis. However, the mechanisms underlying such a role of PKM2 remain elusive. Here we show that PKM2 translocates to mitochondria under oxidative stress. In the mitochondria, PKM2 interacts with and phosphorylates Bcl2 at threonine (T) 69. This phosphorylation prevents the binding of Cul3-based E3 ligase to Bcl2 and subsequent degradation of Bcl2. A chaperone protein, HSP90α1, is required for this function of PKM2. HSP90α1's ATPase activity launches a conformational change of PKM2 and facilitates interaction between PKM2 and Bcl2. Replacement of wild-type Bcl2 with phosphorylation-deficient Bcl2 T69A mutant sensitizes glioma cells to oxidative stress-induced apoptosis and impairs brain tumor formation in an orthotopic xenograft model. Notably, a peptide that is composed of the amino acid residues from 389 to 405 of PKM2, through which PKM2 binds to Bcl2, disrupts PKM2-Bcl2 interaction, promotes Bcl2 degradation and impairs brain tumor growth. In addition, levels of Bcl2 T69 phosphorylation, conformation-altered PKM2 and Bcl2 protein correlate with one another in specimens of human glioblastoma patients. Moreover, levels of Bcl2 T69 phosphorylation and conformation-altered PKM2 correlate with both grades and prognosis of glioma malignancy. Our findings uncover a novel mechanism through which mitochondrial PKM2 phosphorylates Bcl2 and inhibits apoptosis directly, highlight the essential role of PKM2 in ROS adaptation of cancer cells, and implicate HSP90-PKM2-Bcl2 axis as a potential target for therapeutic intervention in glioblastoma.
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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.