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Cited by 78Genetics, Aging, and Longevity in Model OrganismsMitochondrial Function and PathologyAutophagy in Disease and Therapy

The DOI matches its Crossref record; 20 of the 20 references it cites were found in a registry or an index.

The transcriptional coactivator CBP/p300 is an evolutionarily conserved node that promotes longevity in response to mitochondrial stress

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Li, Terytty Yang, Sleiman, Maroun Bou, Li, Hao, Gao, Arwen W., Mottis, Adrienne, Bachmann, Alexis Maximilien, Alam, Gaby El, Li, Xiaoxu, Goeminne, Ludger J. E., Schoonjans, Kristina, Auwerx, Johan·2021·Nature Aging
DOI 10.1038/s43587-020-00025-zPMC PMC7116894
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Abstract

Organisms respond to mitochondrial stress by activating multiple defense pathways including the mitochondrial unfolded protein response (UPR mt). However, how UPR mt regulators are orchestrated to transcriptionally activate stress responses remains largely unknown. Here we identified CBP-1, the worm ortholog of the mammalian acetyltransferases CBP/p300, as an essential regulator of the UPR mt, as well as mitochondrial stress-induced immune response, reduction of amyloid-β aggregation and lifespan extension in Caenorhabditis elegans. Mechanistically, CBP-1 acts downstream of histone demethylases, JMJD-1.2/JMJD-3.1, and upstream of UPR mt transcription factors including ATFS-1, to systematically induce a broad spectrum of UPR mt genes and execute multiple beneficial functions. In mouse and human populations, transcript levels of CBP/p300 positively correlate with UPR mt transcripts and longevity. Furthermore, CBP/p300 inhibition disrupts, while forced expression of p300 is sufficient to activate, the UPR mt in mammalian cells. These results highlight an evolutionarily conserved mechanism that determines mitochondrial stress response, and promotes health and longevity through CBP/p300.

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  • Loss of function of CBP/p300 is associated with familial AD and neuronal apoptosis.

    “and the loss of function of CBP/p300 is associated with familial AD and neuronal apoptosis [117,118,119,120,121].”

    From Rlip76: An Unexplored Player in Neurodegeneration and Alzheimer’s Disease? (2022) · cites this paper as [120]

    The Discussion (page unavailable in our copy) says changes in CBP/p300 function are associated with Alzheimer’s disease, and the Results report that cbp-1 knockdown worsened amyloid-β aggregation in a worm AD model. Neither passage specifies familial AD or links CBP/p300 loss of function to neuronal apoptosis; the worm model expresses amyloid-β in muscle cells. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • CBP/p300 transcriptional co-activators are a conserved mechanism for responding to mitochondrial stress.

    “The CBP/p300 transcriptional co-activators are a conserved mechanism for responding to mitochondrial stress”

    From Rlip76: An Unexplored Player in Neurodegeneration and Alzheimer’s Disease? (2022) · cites this paper as [120]

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Metadata

Authors
Li, T. Y., Sleiman, M. B., Li, H., Gao, A. W., Mottis, A., Bachmann, A. M., Alam, G. E., Li, X., Goeminne, L. J. E., Schoonjans, K., & Auwerx, J.
Affiliations
École Polytechnique Fédérale de Lausanne (CH)
Corresponding author
Auwerx, Johan
ORCID
Venue
Nature Aging
Publisher
Springer Science and Business Media LLC
Published
2021-02-08
Volume
1
Issue
2
Pages
165-178
ISSN
2662-8465 (ISSN-L)
DOI
10.1038/s43587-020-00025-z
PMC
PMC7116894
OpenAlex
W3128901108
Cited by
78
References
20
Citations by year
2026: 12 · 2025: 11 · 2024: 17 · 2023: 13 · 2022: 21 · 2021: 4
FWCI
4.95
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Aging (publishedVersion)
  • PubMed (publishedVersion)
  • Pure Amsterdam UMC (publishedVersion, other-oa)
  • PubMed Central (acceptedVersion)
Funders
Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (179435)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Autophagy in Disease and Therapy
Keywords
CBP/p300, mitochondrial unfolded protein response, mitochondrial stress, longevity, histone demethylase, ATFS-1, amyloid-beta aggregation, lifespan extension, Caenorhabditis elegans, acetyltransferase, healthspan
MeSH terms
Animals, Humans, Longevity, Mammals, Transcription Factors, Caenorhabditis elegans, Cyclic AMP Response Element-Binding Protein, Caenorhabditis elegans Proteins, CREB-Binding Protein, Mice, Histone Acetyltransferases, Histone Demethylases

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