Evaluation of NCLX and MCU functions in the central nervous system

• Grant number: 18/21487-9
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: January 01, 2019
• End date: December 31, 2020
• Field of knowledge: Biological Sciences - Biochemistry - Metabolism and Bioenergetics
• Principal Investigator: Alicia Juliana Kowaltowski
• Grantee: Osvaldo Rodrigues Pereira Junior
• Host Institution: Instituto de Química (IQ). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 13/07937-8 - Redoxome - Redox Processes in Biomedicine, AP.CEPID

Abstract

The central nervous system (CNS) has constant high energy demands to perform a series of specialized processes. Therefore it strongly relies on cellular respiration to supply that energy. Given that, in eukaryotic cells, mitochondria are the main source for ATP production, its importance in CNS cells becomes evident. Another relevant mitochondrial function is cytosolic Ca2+ uptake, as the levels of this ion in the mitochondrial matrix can modulate many functions, such as respiration. In the CNS, the main pathways for Ca2+ transport are the MCU, a uniporter responsible for Ca2+ uptake, and the NCLX, an exchanger responsible for extrusion of mitochondrial Ca2+. Both in neurons and astrocytes, two cellular types of the nervous system, many cellular stimuli are effectors of significant increases in intracellular Ca2+ levels and in ATP demand. However, the physiological role of the metabolic modulation mediated by mitochondrial Ca2+ transporters in the CNS is still not completely elucidated. The goal of this study is to evaluate NCLX and MCU functions through their inhibition by pharmacological modulators CGP-37157 and RuR respectively, regarding cell viability, calcium uptake and lactate secretion, under both basal and cellular stimuli conditions.

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

PEREIRA JR, O. R.; RAMOS, V. M.; CABRAL-COSTA, J. V.; KOWALTOWSKI, A. J.. Changes in mitochondrial morphology modulate LPS-induced loss of calcium homeostasis in BV-2 microglial cells. Journal of Bioenergetics and Biomembranes, v. 53, n. 2, p. 109-118, APR 2021. (19/18402-4, 19/22178-2, 20/06970-5, 17/14713-0, 18/21487-9, 13/07937-8)