Investigation of the mitochondrial unfolded protein response determinants in C. elegans neurons under nutrition deprivation in a high-glucose and/or a high-fat environment

• Grant number: 23/09424-0
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate (Direct)
• Start date: January 26, 2024
• End date: September 19, 2024
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: Eduardo Rochete Ropelle
• Grantee: Fernanda Silva Carneiro
• Supervisor: Mark W Pellegrino
• Host Institution: Faculdade de Ciências Aplicadas (FCA). Universidade Estadual de Campinas (UNICAMP). Limeira , SP, Brazil
• Institution abroad: University of Texas at Arlington (UT Arlington), United States
• Associated to the scholarship: 22/02350-8 - Effect of intermittent fasting on UPRmt in the hypothalamus of obese mice, BP.DD

Abstract

Obesity is a metabolic syndrome caused by an imbalance between energy expenditure and consumption, where the hypothalamus play a major role in appetite control and energy homeostasis. Caenorhabiditis elegans is a nematode that can be as obesity model due they fatty acid metabolism. Mitochondria is an important multifunctional organelle related to energy metabolism through ATP production that also promote homeostasis due an inter-organelle quality control regulation called mitochondrial unfolded protein response (UPR mt ), which is modulated by unfolded or misfolded proteins accumulation, the integrated stress response activation and other potential stressors, that is also dysregulated in obesity conditions. Although the UPR mt activation has significant beneficial effects to promote proteostasis, the persistent activation of this pathway can contribute to damaging consequences, such as mitochondrial dysfunction, neurodegeneration and apoptosis. Considering that the C. elegans neurons has important roles in fat storage and nutrient consumption regulation but the roles during a high-glucose environment is not fully understood, and the nutrient deprivation shows positive effects in both C. elegans and mammalians, this project aims to contribute for unexplored insight about the mitochondrial UPR and ATFS-1 roles during a high-glucose and/or a high-fat environment in C. elegans' neurons, and how the nutrient deprivation can affect this pathway to promote homeostasis.