Mitochondrial ion transporters as sensors and regulators in energy metabolism

• Grant number: 20/06970-5
• Support Opportunities: Research Projects - Thematic Grants
• Start date: February 01, 2021
• End date: January 31, 2027
• Field of knowledge: Biological Sciences - Biochemistry - Metabolism and Bioenergetics
• Principal Investigator: Alicia Juliana Kowaltowski
• Grantee: Alicia Juliana Kowaltowski
• Host Institution: Instituto de Química (IQ). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated researchers: Alexandre Bruni Cardoso ; Eloisa Aparecida Vilas Boas ; Marcus Fernandes de Oliveira ; Sayuri Miyamoto
• Associated research grant(s): 23/00024-9 - Mitochondrial Ca2+/Na+ exchange in cardiac protection against ischemia/reperfusion induced by caloric restriction, AV.BR
• Associated scholarship(s): 24/15581-3 - Effects of mitochondrial calcium transport regulation on amino acid metabolism and urea cycle, BP.DD; 24/00748-0 - Mitochondrial calcium transport and the control of bone and vascular mineralization, BP.PD; 24/07643-9 - Investigation of mitochondrial calcium transport on the modulation of mTORC1 activity mediated by amino acids, BP.IC; + associated scholarships 23/13575-3 - Mitochondrial ion transport and genetic mutations in Parkinson's Disease, BP.PD; 24/03209-2 - Energy Metabolism Regulation by Mitochondrial Ca2+ Transport in the Liver, BP.PD; 22/03975-1 - MODULATION OF NCLX GENE EXPRESSION, BP.IC; 21/04781-3 - Energy metabolism regulation by beta-type estradiol receptor in hepatocytes and adipocytes submitted to energy overload, BP.PD; 21/02481-2 - Energy metabolism regulation by mitochondrial Ca2+ transport in the liver, BP.PD - associated scholarships

Abstract

Mitochondria are the hub of energy metabolism, organelles in which carbohydrate, amino acid and lipid metabolism are completed, and most cellular ATP is produced through oxidative phosphorylation. Because of the dependence on high inner mitochondrial membrane potentials in order to sustain oxidative phosphorylation, ion transport through the inner mitochondrial membrane must be carefully regulated, and has a strong impact on metabolic processes. This project aims to understand how Ca2+ and K+ transport across the inner mitochondrial membrane regulate energy metabolism in mitochondria and the cell. Additionally, we will explore how Ca2+ and K+ transport in mitochondria are affected by nutritional and energetic status. We hope to uncover new mechanisms that regulate energy metabolism and responses to dietary nutritional states. (AU)

Scientific publications

(13)

(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, OSVALDO; KOWALTOWSKI, ALICIA J.. Mitochondrial K+ Transport: Modulation and Functional Consequences. Molecules, v. 26, n. 10, MAY 2021. (20/06970-5, 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)

KOWALTOWSKI, ALICIA J.; ABDULKADER, FERNANDO. How and when to measure mitochondrial inner membrane potentials. BIOPHYSICAL JOURNAL, v. 123, n. 24, p. 8-pg., 2024-12-17. (20/06970-5, 13/07937-8)

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)

RAMOS, VITOR DE MIRANDA; KOWALTOWSKI, ALICIA J.; KAKIMOTO, PAMELA A.. Autophagy in Hepatic Steatosis: A Structured Review. FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY, v. 9, APR 15 2021. (20/06970-5, 13/07937-8, 19/18402-4, 15/25862-0)

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)

BARBOSA DAVID, CICERA EDNA; BRITO LUCAS, ALINE MARIA; OLIVEIRA CUNHA, PEDRO LOURENZO; PONTE VIANA, YUANA IVIA; YOSHINAGA, MARCOS YUKIO; MIYAMOTO, SAYURI; CHAVES FILHO, ADRIANO BRITO; NUNES VARELA, ANNA LIDIA; KOWALTOWSKI, ALICIA JULIANA; FACUNDO, HEBERTY TARSO. alorie restriction changes lipidomic profiles and maintains mitochondrial function and redox balance during isoproterenol-induced cardiac hypertroph. JOURNAL OF PHYSIOLOGY AND BIOCHEMISTRY, v. 78, n. 1, p. 283-294, FEB 2022. (20/06970-5, 13/07937-8)

KOWALTOWSKI, ALICIA J.. Cold Exposure and the Metabolism of Mice, Men, and Other Wonderful Creatures. PHYSIOLOGY, v. 37, n. 5, p. 7-pg., 2022-09-01. (20/06970-5, 13/07937-8)

SERNA, JULIAN D. C.; AMARAL, ANDRESSA G.; CALDEIRA DA SILVA, CAMILLE C.; MUNHOZ, ANA C.; VILAS-BOAS, ELOISA A.; MENEZES-FILHO, SERGIO L.; KOWALTOWSKI, ALICIA J.. Regulation of kidney mitochondrial function by caloric restriction. AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY, v. 323, n. 1, p. 15-pg., 2022-07-01. (19/05226-3, 19/04233-6, 13/07937-8, 20/06970-5)

ROCHA, DEBORA S.; MANUCCI, ANTONIO C.; BRUNI-CARDOSO, ALEXANDRE; KOWALTOWSKI, ALICIA J.; VILAS-BOAS, ELOISA A.. A practical and robust method to evaluate metabolic fluxes in primary pancreatic islets. MOLECULAR METABOLISM, v. 83, p. 13-pg., 2024-04-03. (13/07937-8, 20/06970-5, 21/02481-2, 21/04781-3)

VILAS-BOAS, ELOISA A.; KOWALTOWSKI, ALICIA J.. Mitochondrial redox state, bioenergetics, and calcium transport in caloric restriction: A metabolic nexus. Free Radical Biology and Medicine, v. 219, p. 20-pg., 2024-04-29. (20/06970-5, 13/07937-8, 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)

GHIROTTO, BRUNO; OLIVEIRA, DANYLLO F.; CIPELLI, MARCELLA; BASSO, PAULO J.; LIMA, JEAN; BREDA, CRISTIANE N. S.; RIBEIRO, HENRIQUE C.; SILVA, CAMILLE C. C.; SERTIE, ANDREA L.; OLIVEIRA, ANTONIO EDSON R.; et al. MS-Driven Metabolic Alterations Are Recapitulated in iPSC-Derived Astrocytes. ANNALS OF NEUROLOGY, v. 91, n. 5, p. 18-pg., 2022-03-17. (17/05264-7, 18/23460-0, 13/08028-1, 20/06970-5, 13/07937-8)