Dokument: CoCl₂‐triggered pseudohypoxic stress induces proteasomal degradation of SIRT4 via polyubiquitination of lysines K78 and K299
| Titel: | CoCl₂‐triggered pseudohypoxic stress induces proteasomal degradation of SIRT4 via polyubiquitination of lysines K78 and K299 | |||||||
| URL für Lesezeichen: | https://docserv.uni-duesseldorf.de/servlets/DocumentServlet?id=67302 | |||||||
| URN (NBN): | urn:nbn:de:hbz:061-20241031-121432-4 | |||||||
| Kollektion: | Publikationen | |||||||
| Sprache: | Englisch | |||||||
| Dokumententyp: | Wissenschaftliche Texte » Artikel, Aufsatz | |||||||
| Medientyp: | Text | |||||||
| Autoren: | Hampel, Nils [Autor] Georgy, Jacqueline [Autor] Mehrabipour, Mehrnaz [Autor] Lang, Alexander [Autor] Lehmkuhl, Isabell [Autor] Scheller, Jürgen [Autor] Ahmadian, Mohammad Reza [Autor] Floss, Doreen M. [Autor] Piekorz, Roland P. [Autor] | |||||||
| Dateien: |
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| Stichwörter: | autophagy, SIRT4, sirtuin, pseudohypoxia, proteasome, ubiquitination | |||||||
| Beschreibung: | SIRT4, together with SIRT3 and SIRT5, comprises the mitochondrially localized subgroup of sirtuins. SIRT4 regulates mitochondrial bioenergetics, dynamics (mitochondrial fusion), and quality control (mitophagy) via its NAD+-dependent enzymatic activities. Here, we address the regulation
of SIRT4 itself by characterizing its protein stability and degradation upon CoCl 2 -induced pseudohypoxic stress that typically triggers mitophagy. Interestingly, we observed that of the mitochondrial sirtuins, only the protein levels of SIRT4 or ectopically expressed SIRT4-eGFP decrease upon CoCl 2 treatment of HEK293 cells. Co-treatment with BafA1, an inhibitor of autophagosome–lysosome fusion required for autophagy/mitophagy, or the use of the proteasome inhibitor MG132, prevented CoCl 2 -induced SIRT4 downregulation. Consistent with the proteasomal degradation of SIRT4, the lysine mutants SIRT4(K78R) and SIRT4(K299R) showed significantly reduced polyubiquitination upon CoCl 2 treatment and were more resistant to pseudohypoxia-induced degradation as compared to SIRT4. Moreover, SIRT4(K78R) and SIRT4(K299R) displayed increased basal protein stability as compared to wild-type SIRT4 when subjected to MG132 treatment or cycloheximide (CHX) chase assays. Thus, our data indicate that stress-induced protein degradation of SIRT4 occurs through two mechanisms: (a) via mitochondrial autophagy/mitophagy, and (b) as a separate process via proteasomal degradation within the cytoplasm. | |||||||
| Rechtliche Vermerke: | Originalveröffentlichung:
Hampel, N., Georgy, J., Mehrabipour, M., Lang, A., Lehmkuhl, I., Scheller, J., Ahmadian, M. R., Floß, D. M., & Piekorz, R. P. (2023). CoCl₂‐triggered pseudohypoxic stress induces proteasomal degradation of SIRT4 via polyubiquitination of lysines K78 and K299 [OnlineRessource]. FEBS Open Bio, 13(12), 2187–2199. https://doi.org/10.1002/2211-5463.13715 | |||||||
| Lizenz: |  Dieses Werk ist lizenziert unter einer Creative Commons Namensnennung 4.0 International Lizenz | |||||||
| Fachbereich / Einrichtung: | Medizinische Fakultät | |||||||
| Dokument erstellt am: | 31.10.2024 | |||||||
| Dateien geändert am: | 31.10.2024 |
