Utilize este identificador para referenciar este registo:
https://hdl.handle.net/1822/62310
Título: | α-Synuclein toxicity in yeast and human cells is caused by cell cycle re-entry and autophagy degradation of ribonucleotide reductase 1 |
Outro(s) título(s): | Alpha‐synuclein toxicity in yeast and human cells is caused by cell cycle re-entry and autophagy degradation of ribonucleotide reductase 1 |
Autor(es): | Marques, Maria Belém Sousa Sampaio Guedes, Ana Vasilevskiy, Igor Gonçalves, Susana Outeiro, Tiago F. Winderickx, Joris Burhans, William C. Ludovico, Paula |
Palavras-chave: | Alpha‐synuclein Autophagy Cell cycle re‐entry Chronological aging DNA damage responses Ribonuclease reductase |
Data: | Ago-2019 |
Editora: | Wiley |
Revista: | Aging Cell |
Resumo(s): | α-Synuclein (aSyn) toxicity is associated with cell cycle alterations, activation of DNA damage responses (DDR), and deregulation of autophagy. However, the relationships between these phenomena remain largely unknown. Here, we demonstrate that in a yeast model of aSyn toxicity and aging, aSyn expression induces Ras2-dependent growth signaling, cell cycle re-entry, DDR activation, autophagy, and autophagic degradation of ribonucleotide reductase 1 (Rnr1), a protein required for the activity of ribonucleotide reductase and dNTP synthesis. These events lead to cell death and aging, which are abrogated by deleting RAS2, inhibiting DDR or autophagy, or overexpressing RNR1. aSyn expression in human H4 neuroglioma cells also induces cell cycle re-entry and S-phase arrest, autophagy, and degradation of RRM1, the human homologue of RNR1, and inhibiting autophagic degradation of RRM1 rescues cells from cell death. Our findings represent a model for aSyn toxicity that has important implications for understanding synucleinopathies and other age-related neurodegenerative diseases. |
Tipo: | Artigo |
URI: | https://hdl.handle.net/1822/62310 |
DOI: | 10.1111/acel.12922 |
ISSN: | 1474-9718 |
e-ISSN: | 1474-9726 |
Arbitragem científica: | yes |
Acesso: | Acesso aberto |
Aparece nas coleções: | ICVS - Artigos em revistas internacionais / Papers in international journals |
Ficheiros deste registo:
Ficheiro | Descrição | Tamanho | Formato | |
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Sampaio-Marques et al. Aging Cell.pdf | 2,82 MB | Adobe PDF | Ver/Abrir |