Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Alavian Ghavanini, A.
Protein misfolding and cell death:
From yeast to fly
PhD-Studium (Doctor of Philosophy); Humanmedizin; [ Dissertation ] Medical University of Graz; 2014. pp. 119
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- Autor*innen der Med Uni Graz:
- Alavian Ghavanini Ali
- Betreuer*innen:
- Höfler Gerald
- Altmetrics:
- Abstract:
- Folding of the proteins has a critical role in maintaining cellular homeostasis. Misfolding of different proteins (e.g. modification, oxidation, etc.) can result in onset of various diseases. The text begins with an introduction to protein folding and talks about the links between protein misfolding and cardiovascular complications as well as neurodegenerative diseases followed by a glimpse on how different model organisms contribute to research. The methodology of the whole work is introduced in “material and methods” section. Results are split into two sections: In section one, we will show how Saccharomyces cerevisiae encounters cell death upon contact with hypochlorous acid (HOCl). Several deletion mutants of apoptotic machinery are tested. Among all, we could identify a kex1p-dependent apoptotic pathway that possibly involves specific oxidation-based protein modifications reminiscent of those present in mammalian proteins upon HOCl stress. We found that upon deletion of this protease, yeast could survive the toxic concentrations of HOCl that previously were able to induce death markers. We could also show that this death pathway is through mitochondria. This was confirmed by using yeast strain lacks mitochondrial DNA. We hypothesize that kex1p-glycosylated proteins are prone to be modified by highly reactive hypochlorous leading to programed cell death (PCD). We will also discuss how HOCl changes the expression of different calcium channels, death receptor as well as cathepsins in HL-1 cardiomyocyte. In section two, we will discuss how autophagy is tailored in Drosophila melanogaster to modify a-synuclein aggregation. We will show how Mn+2 – induced death, locomotion impairment, as well as autophagy are modified in a-synuclein expressing flies by spermidine. In the final part, by Immunostaining of the whole brain of a fly, changes in the expression level of active zone proteins by spermidine treatment have been discussed.