Publicação
The role of endoplasmic reticulummitochondria contact sites on mitochondrial permeabilization and regulated cell death induced by acetic acid
| Resumo: | Zones of close membrane apposition function as signaling hubs for interorganelle communication, sustaining organelle homeostasis and exchange of cellular cues. Particularly, endoplasmic reticulum-mitochondria contact sites (ER-MCS) have been the subject of recent scientific interest since the discovery that these structures are disrupted in several pathologies such as cancer and neurodegenerative diseases. Interestingly, these diseases are also characterized by dysregulated apoptosis. Due to the emerging data that correlates ER-MCS function to known events of the apoptotic program, we aimed to dissect this interplay using the yeast Saccharomyces cerevisiae as a model organism. Until recently, the only known tethering complex between ER and mitochondria of this yeast was the ER-mitochondria encounter structure (ERMES). We have previously shown that this organism commits to an apoptotic-like mitochondria-dependent cell death process in response to acetic acid, a frequent byproduct of alcoholic fermentation carried out by S. cerevisiae. Thus, the main aim of this dissertation was to assess the role of the ERMES complex in the mediation of acetic acid-induced regulated cell death. Preliminary analysis revealed a remarkable role of ERMES in the acid stress response and prompted us to further pursue a phenotypical characterization of the cellular alterations underlying this process. Using mutants deficient in components of the ERMES complex and different techniques, from fluorescence microscopy to flow cytometry, we were able to unveil ERMES as a regulator of cell death and, possibly, its own regulators. In all, this work will aid in the understanding of molecular pathways not yet fully disclosed in apoptosis, namely mitochondrial outer membrane permeabilization. These results come with both biomedical and biotechnological interest since they are expected to further encourage the study of ER-MCS in mammalian cell death as well as the development of more resilient yeast strains in industrial processes. |
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| Autores principais: | Martins, Vítor Rafael Miranda |
| Assunto: | Ciências Naturais::Ciências Biológicas |
| Ano: | 2018 |
| País: | Portugal |
| Tipo de documento: | dissertação de mestrado |
| Tipo de acesso: | acesso aberto |
| Instituição associada: | Universidade do Minho |
| Idioma: | inglês |
| Origem: | RepositóriUM - Universidade do Minho |
| Resumo: | Zones of close membrane apposition function as signaling hubs for interorganelle communication, sustaining organelle homeostasis and exchange of cellular cues. Particularly, endoplasmic reticulum-mitochondria contact sites (ER-MCS) have been the subject of recent scientific interest since the discovery that these structures are disrupted in several pathologies such as cancer and neurodegenerative diseases. Interestingly, these diseases are also characterized by dysregulated apoptosis. Due to the emerging data that correlates ER-MCS function to known events of the apoptotic program, we aimed to dissect this interplay using the yeast Saccharomyces cerevisiae as a model organism. Until recently, the only known tethering complex between ER and mitochondria of this yeast was the ER-mitochondria encounter structure (ERMES). We have previously shown that this organism commits to an apoptotic-like mitochondria-dependent cell death process in response to acetic acid, a frequent byproduct of alcoholic fermentation carried out by S. cerevisiae. Thus, the main aim of this dissertation was to assess the role of the ERMES complex in the mediation of acetic acid-induced regulated cell death. Preliminary analysis revealed a remarkable role of ERMES in the acid stress response and prompted us to further pursue a phenotypical characterization of the cellular alterations underlying this process. Using mutants deficient in components of the ERMES complex and different techniques, from fluorescence microscopy to flow cytometry, we were able to unveil ERMES as a regulator of cell death and, possibly, its own regulators. In all, this work will aid in the understanding of molecular pathways not yet fully disclosed in apoptosis, namely mitochondrial outer membrane permeabilization. These results come with both biomedical and biotechnological interest since they are expected to further encourage the study of ER-MCS in mammalian cell death as well as the development of more resilient yeast strains in industrial processes. |
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