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http://doi.org/10.25358/openscience-7586Full metadata record
| DC Field | Value | Language |
|---|---|---|
| dc.contributor.author | Baeken, Marius W. | - |
| dc.contributor.author | Schwarz, Mario | - |
| dc.contributor.author | Kern, Andreas | - |
| dc.contributor.author | Moosmann, Bernd | - |
| dc.contributor.author | Hajieva, Parvana | - |
| dc.contributor.author | Behl, Christian | - |
| dc.date.accessioned | 2022-08-22T09:07:41Z | - |
| dc.date.available | 2022-08-22T09:07:41Z | - |
| dc.date.issued | 2021 | - |
| dc.identifier.uri | https://openscience.ub.uni-mainz.de/handle/20.500.12030/7600 | - |
| dc.description.abstract | The sirtuin (SIRT) protein family has been of major research interest over the last decades because of their involvement in aging, cancer, and cell death. SIRTs have been implicated in gene and metabolic regulation through their capacity to remove acyl groups from lysine residues in proteins in an NAD+-dependent manner, which may alter individual protein properties as well as the histone–DNA interaction. Since SIRTs regulate a wide range of different signaling cascades, a fine-tuned homeostasis of these proteins is imperative to guarantee the function and survival of the cell. So far, however, how exactly this homeostasis is established has remained unknown. Here, we provide evidence that neuronal SIRT degradation in Parkinson’s disease (PD) models is executed by autophagy rather than the proteasome. In neuronal Lund human mesencephalic (LUHMES) cells, all seven SIRTs were substrates for autophagy and showed an accelerated autophagy-dependent degradation upon 1-methyl-4-phenylpyridinium (MPP+) mediated oxidative insults in vitro, whereas the proteasome did not contribute to the removal of oxidized SIRTs. Through blockade of endogenous H2O2 generation and supplementation with the selective radical scavenger phenothiazine (PHT), we could identify H2O2-derived species as the responsible SIRT-oxidizing agents. Analysis of all human SIRTs suggested a conserved regulatory motif based on cysteine oxidation, which may have triggered their degradation via autophagy. High amounts of H2O2, however, rapidly carbonylated selectively SIRT2, SIRT6, and SIRT7, which were found to accumulate carbonylation-prone amino acids. Our data may help in finding new strategies to maintain and modify SIRT bioavailability in neurodegenerative disorders. | en_GB |
| dc.language.iso | eng | de |
| dc.rights | CC BY | * |
| dc.rights.uri | https://creativecommons.org/licenses/by/4.0/ | * |
| dc.subject.ddc | 610 Medizin | de_DE |
| dc.subject.ddc | 610 Medical sciences | en_GB |
| dc.title | The selective degradation of sirtuins via macroautophagy in the MPP+ model of Parkinson’s disease is promoted by conserved oxidation sites | en_GB |
| dc.type | Zeitschriftenaufsatz | de |
| dc.identifier.doi | http://doi.org/10.25358/openscience-7586 | - |
| jgu.type.dinitype | article | en_GB |
| jgu.type.version | Published version | de |
| jgu.type.resource | Text | de |
| jgu.organisation.department | FB 04 Medizin | de |
| jgu.organisation.number | 2700 | - |
| jgu.organisation.name | Johannes Gutenberg-Universität Mainz | - |
| jgu.rights.accessrights | openAccess | - |
| jgu.journal.title | Cell death discovery | de |
| jgu.journal.volume | 7 | de |
| jgu.pages.alternative | 286 | de |
| jgu.publisher.year | 2021 | - |
| jgu.publisher.name | Nature Publishing Group | de |
| jgu.publisher.place | London | de |
| jgu.publisher.issn | 2058-7716 | de |
| jgu.organisation.place | Mainz | - |
| jgu.subject.ddccode | 610 | de |
| jgu.publisher.doi | 10.1038/s41420-021-00683-x | de |
| jgu.organisation.ror | https://ror.org/023b0x485 | - |
| Appears in collections: | JGU-Publikationen | |
Files in This Item:
| File | Description | Size | Format | ||
|---|---|---|---|---|---|
 | the_selective_degradation_of_-20220822110353626.pdf | 4.82 MB | Adobe PDF | View/Open |