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| Author(s): |
Rodrigo Stellzer Gaspar
Total Authors: 1
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| Document type: | Master's Dissertation |
| Press: | Limeira, SP. |
| Institution: | Universidade Estadual de Campinas (UNICAMP). Faculdade de Ciências Aplicadas |
| Defense date: | 2016-11-16 |
| Examining board members: |
Eduardo Rochete Ropelle;
Licio Augusto Velloso;
Augusto Ducati Luchessi
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| Advisor: | Eduardo Rochete Ropelle |
| Abstract | |
The mitochondrial unfolded protein response (UPRmt) is an adaptive stress response, which ensures both integrity and function of proteins by stimulating mitochondrial chaperones (such as HSP60) and mitochondrial proteases (such as ClpP). Mutagenic studies revealed that alterations in the stoichiometric ratio between mtDNA encoded proteins (such as MTCO1) and nDNA OXPHOS subunits of the electron transport chain, such as SDHA or ATP5A, activates the UPRmt. In organisms such as C.elegans and Drosophila, this response enhances mitochondrial function, cell metabolism and longevity through activation of the UPRmt. Pharmacological treatments (such as NAD + boosters or SIRT1 activators) also activate this response, increasing mitochondrial biogenesis and function, oxidative capacity of skeletal muscle and liver and even improves their functional capacity. Although the induction of UPRmt, mediated by mitonuclear imbalance, seems to be a well-conserved biological process among mammals (by increasing the organic function in different tissues), it has not yet been explored if exercise (which increases the NAD+ levels, SIRT1 activity and triggers other pathways promoting mitochondrial biogenesis) is able to activate such stress response. Therefore, the aim of this study was to evaluate the protein content of UPRmt markers and the mitonuclear imbalance in the gastrocnemius of trained mice, as well as mitochondrial function. For this purpose, C57BL/6J mice were allocated into control or trained groups (4 weeks of treadmill running). Skeletal muscle samples were analyzed by Western blotting and mitochondrial respiration. Bioinformatics analysis was performed using genenetwork.org database, with data from skeletal muscle of human and BXD strains. In mice, the UPRmt markers were strongly correlated with mitochondrial genes (also observed in human database) and exercise-related phenotypes, such as RER and locomotor activity. The trained animals increased their exercise performance, their mitochondrial respiration, presented mitonuclear imbalance (2-fold increase in the MTCO1:SDHA ratio) and increased ClpP protein content. This project can assist in understanding the role of UPRmt on several exercise-induced adaptations and provide useful knowledge for future therapies targetting diseases related to mitochondrial dysfunction (AU) | |
| FAPESP's process: | 15/06463-8 - Role of Physical Training in the UPRmt |
| Grantee: | Rodrigo Stellzer Gaspar |
| Support Opportunities: | Scholarships in Brazil - Master |