Effects of mitochondrial calcium transport regulation in autophagic process of hepatocytes

• Grant number: 19/18402-4
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: December 01, 2019
• End date: July 31, 2024
• Field of knowledge: Biological Sciences - Biochemistry - Metabolism and Bioenergetics
• Principal Investigator: Alicia Juliana Kowaltowski
• Grantee: Vitor de Miranda Ramos
• 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): 22/08581-1 - Mitochondrial calcium transport in nutrient sensing: does NCLX regulate mTORC1 activity?, BE.EP.DR

Abstract

Autophagy is a fundamental process which regulates the structural and energetic homeostasis of the cell. Recently, many studies indicate a role for intracellular calcium signaling in the regulation of autophagic flux. Additionally, mitochondria are known to actively transport calcium, and have a direct role in calcium signaling. However, the relationship between mitochondria and calcium regulation of autophagy has not been explored yet. Hepatic cells have a central role in the metabolic homeostasis in humans, and autophagy is a mechanism of extreme importance for the physiology and protection of these cells. Therefore, we chose hepatocytes as an experimental model. The aim of this project is to investigate the role of mitochondria in the regulation of autophagy and mitophagy by calcium signaling. To this end, the participation of three major factor that regulate mitochondrial calcium will be evaluated: (1) influx and efflux membrane transporters; (2) fusion and mission morphology modulation and (3) mitochondrial membrane potentials (”Èm). Overall, this project intents to contribute toward a better understanding of autophagy regulation mechanisms, correlating it with other fundamental process within the cell. (AU)

Scientific publications

(4)

(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)

KAKIMOTO, PAMELA A.; SERNA, JULIAN DAVID C.; RAMOS, VITOR DE MIRANDA; ZORZANO, ANTONIO; KOWALTOWSKI, ALICIA J.. Increased glycolysis is an early consequence of palmitate lipotoxicity mediated by redox signaling. REDOX BIOLOGY, v. 45, SEP 2021. (19/18402-4, 13/07937-8, 15/25862-0, 19/05226-3)

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)

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)

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)