mitoKATP channels and matrix volume regulation in mitochondrial dynamics in the liver.

• Grant number: 23/04340-2
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: June 01, 2023
• End date: December 31, 2024
• Field of knowledge: Biological Sciences - Biochemistry - Metabolism and Bioenergetics
• Principal Investigator: Eloisa Aparecida Vilas Boas
• Grantee: Lucas Rafael Pereira Camara
• Host Institution: Instituto de Química (IQ). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Mitochondria are organelles responsible for the efficient generation of ATP through the metabolism of carbohydrates, lipids and proteins. They are dynamic organelles, which undergo a constant change in size and shape over time, through mitochondrial fusion and fission processes. The mitochondrial inner membrane has a negative internal potential, essential to sustain oxidative phosphorylation. Therefore, ion transport across the inner mitochondrial membrane must be carefully regulated and has a strong impact on metabolic processes.Potassium (K+) is an ion that maintains and regulates several basic functions of cells, being of great importance in the stability of cell space and volume. The combination of an intracellular environment rich in K+ and a mitochondrial membrane electrochemical potential, which provides an electrostatically negative environment, allows K+ to enter the mitochondrial matrix through leakage. Furthermore, K+ entry into the mitochondrial matrix can also occur through mitoKATP channels. The entry of this ion is accompanied by an obligatory osmotic process, resulting in swelling of the organelle. In contrast, the output of K+ from the matrix occurs through the K+/H+ exchanger. It is known that K+ cycling in mitochondria does not significantly decrease membrane potentials, so the main effect of mito KATP activity must be the regulation of mitochondrial volume.Our group has already shown that some situations that lead to changes in mitochondrial morphology in the liver are associated with increased mitoKATP activity, such as during nutrient overload. Therefore, this project aims to understand how mitoKATP activity helps maintain the architecture and homeostasis associated with mitochondrial dynamics in the liver. It is hypothesized that changes in mitochondrial size, dynamics and shape, modulated by these channels, require changes in K+ transport across the inner membrane to maintain matrix volume.