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- Title
Neuroserpin Inclusion Bodies in a FENIB Yeast Model.
- Authors
Vapore, Valentina; Mazzaglia, Corrado; Sibilia, Diego; Del Vecchio, Mara; Fruhmann, Gernot; Valenti, Marta; Miranda, Elena; Rinaldi, Teresa; Winderickx, Joris; Mazzoni, Cristina
- Abstract
FENIB (familial encephalopathy with neuroserpin inclusion bodies) is a human monogenic disease caused by point mutations in the SERPINI1 gene, characterized by the intracellular deposition of polymers of neuroserpin (NS), which leads to proteotoxicity and cell death. Despite the different cell and animal models developed thus far, the exact mechanism of cell toxicity elicited by NS polymers remains unclear. Here, we report that human wild-type NS and the polymerogenic variant G392E NS form protein aggregates mainly localized within the endoplasmic reticulum (ER) when expressed in the yeast S. cerevisiae. The expression of NS in yeast delayed the exit from the lag phase, suggesting that NS inclusions cause cellular stress. The cells also showed a higher resistance following mild oxidative stress treatments when compared to control cells. Furthermore, the expression of NS in a pro-apoptotic mutant strain-induced cell death during aging. Overall, these data recapitulate phenotypes observed in mammalian cells, thereby validating S. cerevisiae as a model for FENIB.
- Subjects
CELLULAR inclusions; CELL death; YEAST; ENDOPLASMIC reticulum; PHENOTYPES; OXIDATIVE stress
- Publication
Microorganisms, 2021, Vol 9, Issue 7, p1498
- ISSN
2076-2607
- Publication type
Article
- DOI
10.3390/microorganisms9071498