Regulation of mitochondrial calcium transport by glucose in NRK cell line of rat kidney

• Grant number: 21/13933-1
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: February 01, 2022
• End date: January 31, 2023
• Field of knowledge: Biological Sciences - Biochemistry - Metabolism and Bioenergetics
• Principal Investigator: Alicia Juliana Kowaltowski
• Grantee: Georgia Ohya
• Host Institution: Instituto de Química (IQ). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Ca2+ regulates several aspects of cell behavior, including mitochondrial function. Ca2+ activates several enzymes involved in the tricarboxylic acid cycle, as well as proteins involved in the transport of oxidable substrates. Physiological Ca2+concentrations lead to an increase in the rate of oxidative phosphorylation, and in the production rate of reactive oxygen species (ROS) under certain conditions. The electrophoretic uptake of Ca2+ by mitochondria is supported by the mitochondrial membrane potential (Ӭ). The MCU complex (MCUc) provides the most important route for Ca2+ uptake. The composition of this complex is plastic, and varies in an organ-dependent manner, playing a key role in the kinetics of Ca2+ uptake. The composition of the MCUc is altered in different pathological contexts, like cancer and diabetes, and also, in response to diet. The molecular mechanisms behind these changes are poorly understood. In the present work, it will be established an in-vitro model to determine the effect of glucose concentration in the culture media on mitochondrial function, with an emphasis on Ca2+ transport. For this purpose, we will evaluate the kinetics of Ca2+ uptake and the sensitivity to Ca2+-induced mitochondrial permeability transition in NRK cells exposed to normal (5,5 mM), medium (12,5 mM), and high (25 mM) glucose concentrations. These parameters will be correlated with alterations in the composition of MCUc and possible bioenergetic and redox alterations. Taken together, these results will allow us to characterize the effect of physiological and supraphysiological glucose concentrations on mitochondrial calcium transport and their functional consequences. (AU)