ArticleThe Journal of cell biology2003
Mitochondria to nucleus stress signaling: a distinctive mechanism of NFkappaB/Rel activation through calcineurin-mediated inactivation of IkappaBbeta.
Article in The Journal of cell biology, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 87 papers, 1 of them a synthesis that pooled it.
What it found
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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.
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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.
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Who cites it
87 citing papers in PubMed, 1 synthesis or guideline pooled it, 172 citations in OpenAlex.
- Altered mitochondrial DNA copy number contributes to human cancer risk: evidence from an updated meta-analysis.Scientific reports · 2016Pooled it
- Metabolites with a message: impacts on epigenetics and implications for epimetabopathies.EMBO reports · 2026Review
- Aging and Peripheral Nerve Injuries: Impaired Repair, Inflammaging Impact, and Regeneration Resistance.Biomedicines · 2026Review
- Absence of IκBβ/NFκB signaling does not attenuate acetaminophen-induced hepatic injury.Anatomical record (Hoboken, N.J. : 2007) · 2025Article
- Mechanisms and therapeutic perspectives of mitochondrial dysfunction of macrophages in periodontitis.Frontiers in cellular and infection microbiology · 2025Review
- The Emerging Role of the Mitochondrial Respiratory Chain in Skeletal Aging.Aging and disease · 2024Review
- Principles and functions of metabolic compartmentalization.Nature metabolism · 2022Review
- Insights regarding mitochondrial DNA copy number alterations in human cancer (Review).International journal of molecular medicine · 2022Review
- Insights into the Pathogenesis of Neurodegenerative Diseases: Focus on Mitochondrial Dysfunction and Oxidative Stress.International journal of molecular sciences · 2021Review
- Mitochondrial dysfunction, UPRCell & bioscience · 2021Review
- Lower threshold to NFκB activity sensitizes murine β-cells to streptozotocin.The Journal of endocrinology · 2021Article
- Control of Murine Primordial Follicle Growth Activation by IκB/NFκB Signaling.Reproductive sciences (Thousand Oaks, Calif.) · 2020Article
- Mitonuclear Interactions in the Maintenance of Mitochondrial Integrity.Life (Basel, Switzerland) · 2020Review
- Mitochondrial retrograde signalling in neurological disease.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2020Article
- Role of the mitochondrial stress response in human cancer progression.Experimental biology and medicine (Maywood, N.J.) · 2020Review
- CpG-ODN-mediated TLR9 innate immune signalling and calcium dyshomeostasis converge on the NFκB inhibitory protein IκBβ to drive IL1α and IL1β expression.Immunology · 2020Article
- Cytochrome c oxidase dysfunction enhances phagocytic function and osteoclast formation in macrophages.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019Article
- The secret messages between mitochondria and nucleus in muscle cell biology.Archives of biochemistry and biophysics · 2019Review
- Review
- Mitochondrial biology and prostate cancer ethnic disparity.Carcinogenesis · 2018Review
27 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 2 institutions in 1 country.
Funding
Abstract
Mitochondrial genetic and metabolic stress causes activation of calcineurin (Cn), NFAT, ATF2, and NFkappaB/Rel factors, which collectively alter the expression of an array of nuclear genes. We demonstrate here that mitochondrial stress-induced activation of NFkappaB/Rel factors involves inactivation of IkappaBbeta through Cn-mediated dephosphorylation. Phosphorylated IkappaBbeta is a substrate for Cn phosphatase, which was inhibited by FK506 and RII peptide. Chemical cross-linking and coimmunoprecipitation show that NFkappaB/Rel factor-bound IkappaBbeta forms a ternary complex with Cn under in vitro and in vivo conditions that was sensitive to FK506. Results show that phosphorylation at S313 and S315 from the COOH-terminal PEST domain of IkappaBbeta is critical for binding to Cn. Mutations at S313/S315 of IkappaBbeta abolished Cn binding, inhibited Cn-mediated increase of Rel proteins in the nucleus, and had a dominant-negative effect on the mitochondrial stress-induced expression of RyR1 and cathepsin L genes. Our results show the distinctive nature of mitochondrial stress-induced NFkappaB/Rel activation, which is independent of IKKalpha and IKKbeta kinases and affects gene target(s) that are different from cytokine and TNFalpha-induced stress signaling. The results provide new insights into the role of Cn as a critical link between Ca2+ signaling and NFkappaB/Rel activation.
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What OpenQuestion holds
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.