Autophagy protects against de novo formation of the [PSI+] prion in yeast
| Autor: | Shaun H. Speldewinde, Chris M. Grant |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
0301 basic medicine
autophagy Saccharomyces cerevisiae Proteins Prions Spermidine animal diseases Applied Microbiology Cell Biosynthesis and Biodegradation Saccharomyces cerevisiae Protein aggregation yeast Biochemistry Genetics and Molecular Biology (miscellaneous) Applied Microbiology and Biotechnology Microbiology 03 medical and health sciences chemistry.chemical_compound Virology Gene Expression Regulation Fungal Organelle medicine Genetics oxidative stress Humans lcsh:QH301-705.5 Molecular Biology Autophagy Neurodegenerative Diseases Cell Biology Articles Yeast Cell biology nervous system diseases 030104 developmental biology medicine.anatomical_structure chemistry lcsh:Biology (General) Mutation Parasitology Polyamine Flux (metabolism) Oxidation-Reduction Peptide Termination Factors |
| Zdroj: | Microbial Cell Molecular Biology of the Cell Microbial Cell, Vol 3, Iss 1, Pp 46-48 (2015) |
| ISSN: | 2311-2638 |
| Popis: | The molecular basis by which prions arise spontaneously is poorly understood. The present data point toward oxidative protein damage as one of the triggers of de novo prion formation. Autophagy functions to clear oxidatively damaged proteins before their conversion to the prion form. Prions are self-propagating, infectious proteins that underlie several neurodegenerative diseases. The molecular basis underlying their sporadic formation is poorly understood. We show that autophagy protects against de novo formation of [PSI+], which is the prion form of the yeast Sup35 translation termination factor. Autophagy is a cellular degradation system, and preventing autophagy by mutating its core components elevates the frequency of spontaneous [PSI+] formation. Conversely, increasing autophagic flux by treating cells with the polyamine spermidine suppresses prion formation in mutants that normally show a high frequency of de novo prion formation. Autophagy also protects against the de novo formation of another prion, namely the Rnq1/[PIN+] prion, which is not related in sequence to the Sup35/[PSI+] prion. We show that growth under anaerobic conditions in the absence of molecular oxygen abrogates Sup35 protein damage and suppresses the high frequency of [PSI+] formation in an autophagy mutant. Autophagy therefore normally functions to remove oxidatively damaged Sup35, which accumulates in cells grown under aerobic conditions, but in the absence of autophagy, damaged/misfolded Sup35 undergoes structural transitions favoring its conversion to the propagatable [PSI+] form. |
| Databáze: | OpenAIRE |
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