ArticleExperimental cell research2008
PGAM5 tethers a ternary complex containing Keap1 and Nrf2 to mitochondria.
Article in Experimental cell research, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 173 papers.
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Who cites it
173 citing papers in PubMed, 299 citations in OpenAlex.
- ZO-2 blocks the localization of PGAM5 protein to the mitochondrial membrane and suppresses pancreatic cancer malignancy through metabolic reprogramming.Genes & diseases · 2027Article
- Hydrogen peroxide sensing and signaling in physiology and disease: implications for therapy.Signal transduction and targeted therapy · 2026Review
- The Discovery of GSK3227634: A Potent Inhaled Inhibitor of the KEAP1/NRF2 Protein-Protein Interaction for the Treatment of Chronic Obstructive Pulmonary Disease.Journal of medicinal chemistry · 2026Article
- Targeted degradation of hepatic KEAP1 mitigates drug-induced liver injury via dual boosting NRF2 and PGAM5 signaling.Redox biology · 2026Article
- TRIM25 facilitates mitochondrial dysfunction and extracellular matrix degradation by enhancing USP7-driven ENO1 deubiquitination during intervertebral disc degeneration.Clinical and translational medicine · 2026Article
- Article
- Amyloid precursor protein interacts with the mitochondrial phosphatase PGAM5 and regulates mitochondrial respiration.bioRxiv : the preprint server for biology · 2026Article
- Dose-Related Structural and Functional Modifications of Mitochondria Are Induced In Vitro by Low Ozone Concentrations.International journal of molecular sciences · 2026Article
- Effects of the Pharmacological Modulation of NRF2 in Cancer Progression.Medicina (Kaunas, Lithuania) · 2025Review
- PGAM5 cleavage and oligomerization equilibrates mitochondrial dynamics under stress by regulating DRP1 function.Journal of cell science · 2025Article
- Review
- Role of oxeiptosis in disease mechanisms and therapeutic opportunities.Apoptosis : an international journal on programmed cell death · 2025Review
- Article
- OAB-14 Attenuated Glymphatic System Disorder, Neuroinflammation and Dyskinesia in Parkinson's Disease Model Mice Induced by Rotenone.Neurochemical research · 2025Article
- Health position paper and redox perspectives - Bench to bedside transition for pharmacological regulation of NRF2 in noncommunicable diseases.Redox biology · 2025Review
- ROS-induced cytosolic release of mitochondrial PGAM5 promotes colorectal cancer progression by interacting with MST3.Nature communications · 2025Article
- The dual role of PGAM5 in inflammation.Experimental & molecular medicine · 2025Review
- KEAP1-NRF2 Interaction in Cancer: Competitive Interactors and Their Role in Carcinogenesis.Cancers · 2025Review
- Ferroptosis triggers mitochondrial fragmentation via Drp1 activation.Cell death & disease · 2025Article
- The protective effect and mechanism of dexmedetomidine in inhibiting ferroptosis.Frontiers in pharmacology · 2025Review
113 more citing papers are in PubMed but not listed here.
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Eukaryote cells balance production of reactive oxygen species (ROS) with levels of anti-oxidant enzyme activity to maintain cellular redox homeostasis. Mitochondria are a major source of ROS, while many anti-oxidant genes are regulated by the Nrf2 transcription factor. Keap1, a redox-regulated substrate adaptor for a cullin-based ubiquitin ligase, targets Nrf2 for proteosome-mediated degradation and represses Nrf2-dependent gene expression. We have previously identified a member of the phosphoglycerate mutase family, PGAM5, as a Keap1-binding protein. In this report, we demonstrate that PGAM5 is targeted to the outer membrane of mitochondria by an N-terminal mitochondrial-localization sequence. Furthermore, we provide evidence that PGAM5 forms a ternary complex containing both Keap1 and Nrf2, in which the dimeric Keap1 protein simultaneously binds both PGAM5 and Nrf2 through their conserved E(S/T)GE motifs. Knockdown of either Keap1 or PGAM5 activates Nrf2-dependent gene expression. We suggest that this ternary complex provides a molecular framework for understanding how nuclear anti-oxidant gene expression is regulated in response to changes in mitochondrial function(s).
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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.