Mitochondrial Ca2+ Handling in the Central Nervous System and Energy Metabolism Regulation

• Grant number: 17/14713-0
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: April 01, 2018
• End date: August 29, 2022
• Field of knowledge: Biological Sciences - Biochemistry - Metabolism and Bioenergetics
• Principal Investigator: Alicia Juliana Kowaltowski
• Grantee: João Victor Cabral Costa
• 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
• Associated scholarship(s): 19/22178-2 - NCLX in astrocytic function: metabolism and neuronal homeostasis, BE.EP.DR

Abstract

Ca2+ is an ion of utmost importance for the maintenance of numerous processes in the central nervous system (CNS), including neuronal development and synaptic communication and plasticity. In the mitochondrial matrix, Ca2+ induces the activity of many enzymes associated with energy metabolism, thus coupling ATP production to energetic demands under different stimuli. Hence, mitochondrial Ca2+ transport - in particular the influx through the mitochondrial calcium uniporter (MCU) and efflux through the mitochondrial Na+/Ca2+ exchanger (NCLX) - comprises a critical metabolic regulation point. Cell types across the CNS present diverse metabolic profiles, although they might be tightly coupled, as is the case of neurons and astrocytes. However, these processes are yet to be fully characterized. Therefore, this project aims to evaluate metabolic regulation exerted by the mitochondrial Ca2+ handling system, thus contributing to a better understanding of the interaction between energy metabolism and the CNS.

Scientific publications

(7)

(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)

CABRAL-COSTA, JOAO VICTOR; KOWALTOWSKI, ALICIA J.. Mitochondrial Ca2+ handling as a cell signaling hub: lessons from astrocyte function. ESSAYS IN BIOCHEMISTRY, v. 67, n. 1, p. 13-pg., 2023-03-01. (13/07937-8, 20/06970-5, 17/14713-0, 19/22178-2)

VILAS-BOAS, ELOISA A.; CABRAL-COSTA, JOAO VICTOR; RAMOS, VITOR M.; DA SILVA, CAMILLE C. CALDEIRA; KOWALTOWSKI, ALICIA J.. Goldilocks calcium concentrations and the regulation of oxidative phosphorylation: Too much, too little, or just right. Journal of Biological Chemistry, v. 299, n. 3, p. 17-pg., 2023-02-10. (17/14713-0, 13/07937-8, 19/18402-4, 21/02481-2)

RAMOS, VITOR M.; SERNA, JULIAN D. C.; VILAS-BOAS, ELOISA A.; CABRAL-COSTA, JOAO VICTOR; CUNHA, FERNANDA M.; KATAURA, TETSUSHI; KOROLCHUK, VIKTOR I.; KOWALTOWSKI, ALICIA J.. Mitochondrial sodium/calcium exchanger (NCLX) regulates basal and starvation-induced autophagy through calcium signaling. FASEB JOURNAL, v. 38, n. 3, p. 16-pg., 2024-02-15. (21/02481-2, 19/05226-3, 22/08581-1, 20/06970-5, 13/07937-8, 17/14713-0, 19/18402-4)

KOWALTOWSKI, ALICIA J.; MENEZES-FILHO, SERGIO L.; ASSALI, ESSAM A.; GONCALVES, ISABELA G.; CABRAL-COSTA, JOAO VICTOR; ABREU, PHABLO; MILLER, NATHANAEL; NOLASCO, PATRICIA; LAURINDO, FRANCISCO R. M.; BRUNI-CARDOSO, ALEXANDRE; et al. Mitochondrial morphology regulates organellar Ca2+ uptake and changes cellular Ca2+ homeostasis. FASEB JOURNAL, v. 33, n. 12, p. 13176-13188, DEC 2019. (16/18633-8, 14/24511-7, 13/07937-8, 17/14713-0)

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)

CABRAL-COSTA, JOAO VICTOR; VICENTE-GUTIERREZ, CARLOS; AGULLA, JESUS; LAPRESA, REBECA; ELROD, JOHN W.; ALMEIDA, ANGELES; BOLANOS, JUAN P.; KOWALTOWSKI, ALICIA J.. Mitochondrial sodium/calcium exchanger NCLX regulates glycolysis in astrocytes, impacting on cognitive performance. Journal of Neurochemistry, v. N/A, p. 15-pg., 2023-01-09. (13/07937-8, 17/14713-0, 20/06970-5, 19/22178-2)

CABRAL-COSTA, J. V.; KOWALTOWSKI, A. J.. Neurological disorders and mitochondria. MOLECULAR ASPECTS OF MEDICINE, v. 71, FEB 2020. (17/14713-0, 13/07937-8)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

COSTA, João Victor Cabral. Mitochondrial Ca2+ Handling in the Central Nervous System: the role of the mitochondrial Na+/Ca2+ exchanger (NCLX) in astrocyte metabolism and function. 2022. Doctoral Thesis - Universidade de São Paulo (USP). Conjunto das Químicas (IQ e FCF) (CQ/DBDCQ) São Paulo.