N1-methylation of adenosine (m1A) in ND5 mRNA leads to complex I dysfunction in Alzheimer’s disease

  1. Jörg, Marko
  2. Plehn, Johanna E.
  3. Kristen, Marco
  4. Lander, Marc ORCID logo
  5. Walz, Lukas
  6. Lietz, Christine
  7. Wijns, Julie
  8. Pichot, Florian
  9. Rojas-Charry, Liliana
  10. Wirtz Martin, Katja M.
  11. Ruffini, Nicolas
  12. Kreim, Nastasja
  13. Gerber, Susanne ORCID logo
  14. Motorin, Yuri
  15. Endres, Kristina ORCID logo
  16. Rossmanith, Walter
  17. Methner, Axel
  18. Helm, Mark
  19. Friedland, Kristina ORCID logo

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1000 Titel
  • N1-methylation of adenosine (m1A) in ND5 mRNA leads to complex I dysfunction in Alzheimer’s disease
1000 Autor/in
  1. Jörg, Marko |
  2. Plehn, Johanna E. |
  3. Kristen, Marco |
  4. Lander, Marc |
  5. Walz, Lukas |
  6. Lietz, Christine |
  7. Wijns, Julie |
  8. Pichot, Florian |
  9. Rojas-Charry, Liliana |
  10. Wirtz Martin, Katja M. |
  11. Ruffini, Nicolas |
  12. Kreim, Nastasja |
  13. Gerber, Susanne |
  14. Motorin, Yuri |
  15. Endres, Kristina |
  16. Rossmanith, Walter |
  17. Methner, Axel |
  18. Helm, Mark |
  19. Friedland, Kristina |
1000 Verlag Nature Publishing Group UK
1000 Erscheinungsjahr 2024
1000 Publikationstyp
  1. Artikel |
1000 Online veröffentlicht
  • 2024-01-29
1000 Erschienen in
1000 Quellenangabe
  • 29(5):1427-1439
1000 Copyrightjahr
  • 2024
1000 Lizenz
1000 Verlagsversion
  • https://doi.org/10.1038/s41380-024-02421-y |
  • https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11189808/ |
1000 Publikationsstatus
1000 Begutachtungsstatus
1000 Sprache der Publikation
1000 Abstract/Summary
  • <jats:title>Abstract</jats:title><jats:p>One mechanism of particular interest to regulate mRNA fate post-transcriptionally is mRNA modification. Especially the extent of m<jats:sup>1</jats:sup>A mRNA methylation is highly discussed due to methodological differences. However, one single m<jats:sup>1</jats:sup>A site in mitochondrial ND5 mRNA was unanimously reported by different groups. ND5 is a subunit of complex I of the respiratory chain. It is considered essential for the coupling of oxidation and proton transport. Here we demonstrate that this m<jats:sup>1</jats:sup>A site might be involved in the pathophysiology of Alzheimer’s disease (AD). One of the pathological hallmarks of this neurodegenerative disease is mitochondrial dysfunction, mainly induced by Amyloid β (Aβ). Aβ mainly disturbs functions of complex I and IV of the respiratory chain. However, the molecular mechanism of complex I dysfunction is still not fully understood. We found enhanced m<jats:sup>1</jats:sup>A methylation of ND5 mRNA in an AD cell model as well as in AD patients. Formation of this m<jats:sup>1</jats:sup>A methylation is catalyzed by increased TRMT10C protein levels, leading to translation repression of ND5. As a consequence, here demonstrated for the first time, TRMT10C induced m<jats:sup>1</jats:sup>A methylation of ND5 mRNA leads to mitochondrial dysfunction. Our findings suggest that this newly identified mechanism might be involved in Aβ-induced mitochondrial dysfunction.</jats:p>
1000 Sacherschließung
lokal Aged, 80 and over [MeSH]
lokal Aged [MeSH]
lokal Adenosine/metabolism [MeSH]
lokal /38/90
lokal /692/699/476
lokal /96/109
lokal Electron Transport Complex I/genetics [MeSH]
lokal Male [MeSH]
lokal Mitochondrial Proteins/genetics [MeSH]
lokal /82/58
lokal Alzheimer Disease/metabolism [MeSH]
lokal RNA, Messenger/metabolism [MeSH]
lokal /13/89
lokal Female [MeSH]
lokal Mitochondrial Proteins/metabolism [MeSH]
lokal /82/80
lokal Methylation [MeSH]
lokal Mitochondria/metabolism [MeSH]
lokal Amyloid beta-Peptides/metabolism [MeSH]
lokal Humans [MeSH]
lokal Electron Transport Complex I/metabolism [MeSH]
lokal /631/45
lokal /38/71
lokal Article
lokal Methyltransferases/genetics [MeSH]
lokal Alzheimer Disease/genetics [MeSH]
lokal Methyltransferases/metabolism [MeSH]
lokal article
1000 Fächerklassifikation (DDC)
1000 Liste der Beteiligten
  1. https://frl.publisso.de/adhoc/uri/SsO2cmcsIE1hcmtv|https://frl.publisso.de/adhoc/uri/UGxlaG4sIEpvaGFubmEgRS4=|https://frl.publisso.de/adhoc/uri/S3Jpc3RlbiwgTWFyY28=|https://orcid.org/0000-0002-2653-6132|https://frl.publisso.de/adhoc/uri/V2FseiwgTHVrYXM=|https://frl.publisso.de/adhoc/uri/TGlldHosIENocmlzdGluZQ==|https://frl.publisso.de/adhoc/uri/V2lqbnMsIEp1bGll|https://frl.publisso.de/adhoc/uri/UGljaG90LCBGbG9yaWFu|https://frl.publisso.de/adhoc/uri/Um9qYXMtQ2hhcnJ5LCBMaWxpYW5h|https://frl.publisso.de/adhoc/uri/V2lydHogTWFydGluLCBLYXRqYSBNLg==|https://frl.publisso.de/adhoc/uri/UnVmZmluaSwgTmljb2xhcw==|https://frl.publisso.de/adhoc/uri/S3JlaW0sIE5hc3Rhc2ph|https://orcid.org/0000-0001-9513-0729|https://frl.publisso.de/adhoc/uri/TW90b3JpbiwgWXVyaQ==|https://orcid.org/0000-0002-1099-8287|https://frl.publisso.de/adhoc/uri/Um9zc21hbml0aCwgV2FsdGVy|https://frl.publisso.de/adhoc/uri/TWV0aG5lciwgQXhlbA==|https://frl.publisso.de/adhoc/uri/SGVsbSwgTWFyaw==|https://orcid.org/0000-0001-8603-5957
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