The DOI matches its Crossref record; 82 of the 82 references it cites were found in a registry or an index.
PGAM5 tethers a ternary complex containing Keap1 and Nrf2 to mitochondria
Open accessAbstract
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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“Interestingly, PGAM5 can recruit both Keap1 and Nrf2 to the outer mitochondrial membrane by binding to one molecule of a Keap1 dimer while simultaneously binding Nrf2 to form a ternary Keap1-PGAM5-Nrf2 complex [102,103]. Interestingly, this results in the stress-induced Keap1-mediated ubiquitination and degradation of not Nrf2, but of mitochondrial Rho GTPase 2 (Miro2), a mitochondrial GTPase inv”
From Nrf2 and Oxidative Stress: A General Overview of Mechanisms and Implications in Human Disease (2022) · cites this paper as [102]
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Role of nrf2 in oxidative stress and toxicity
Ma, Q. (2013) · Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev-pharmtox-011112-140320 · Cited by 4,903
Transcriptional Regulation by Nrf2
Tonelli, C., Chio, I. I. C., & Tuveson, D. A. (2017) · Antioxidants and Redox Signaling · doi:10.1089/ars.2017.7342 · Cited by 2,280
The Nrf2 regulatory network provides an interface between redox and intermediary metabolism
Hayes, J. D., & Dinkova‐Kostova, A. T. (2014) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2014.02.002 · Cited by 2,210
Reactive oxygen species and mitochondria: A nexus of cellular homeostasis
Dunn, J. D., Álvarez, L., Zhang, X., & Soldati, T. (2015) · Redox Biology · doi:10.1016/j.redox.2015.09.005 · Cited by 1,233
Proteasomal and Autophagic Degradation Systems
Đikić, I. (2017) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-061516-044908 · Cited by 1,217
Metadata
- Authors
- Lo, S.-C., & Hannink, M.
- Affiliations
- University of Missouri (US)
- Corresponding author
- Hannink, Mark
- Venue
- Experimental Cell Research
- Publisher
- Elsevier BV
- Published
- 2008-05
- Volume
- 314
- Issue
- 8
- Pages
- 1789-1803
- ISSN
- 0014-4827 (ISSN-L)
- PMC
- PMC2409987
- OpenAlex
- W1974124666
- Cited by
- 300
- References
- 82
- Citations by year
- 2026: 10 · 2025: 13 · 2024: 19 · 2023: 22 · 2022: 22 · 2021: 29 · 2020: 29 · 2019: 15 · 2018: 18 · 2017: 17 · 2016: 19 · 2015: 17 · 2014: 16 · 2013: 14 · 2012: 17
- FWCI
- 2.88
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- Experimental Cell Research (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (1 RO1 AT003389)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics, phytochemicals, and oxidative stress
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Glutathione Transferases and Polymorphisms
- Keywords
- PGAM5, Keap1, Nrf2, ternary complex, mitochondrial outer membrane, redox homeostasis, reactive oxygen species, antioxidant gene expression, proteasomal degradation
- MeSH terms
- Kelch-Like ECH-Associated Protein 1, Amino Acid Sequence, Animals, Carrier Proteins, Cell Line, Cell Nucleus, Gene Expression Regulation, Humans, Mitochondria, Molecular Sequence Data, Phosphoglycerate Mutase, Phosphoprotein Phosphatases, Protein Isoforms, Protein Sorting Signals, Mitochondrial Proteins, Intracellular Signaling Peptides and Proteins, NF-E2-Related Factor 2
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