Structural and functional characterization of mitochondrial protein phosphatases by redox metabolism and their role in cell biology

• Grant number: 19/02605-3
• Support Opportunities: Research Grants - Young Investigators Grants
• Start date: December 01, 2020
• End date: November 30, 2026
• Field of knowledge: Biological Sciences - Biochemistry - Chemistry of Macromolecules
• Principal Investigator: Luciana Elena de Souza Fraga Machado
• Grantee: Luciana Elena de Souza Fraga Machado
• Host Institution: Instituto de Química (IQ). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated researchers: Fernanda Marques da Cunha ; Frederico José Gueiros Filho ; Luis Eduardo Soares Netto
• Associated scholarship(s): 23/16614-0 - Characterization and biochemical and structural analysis of the mitochondrial protein phosphatase PGAM5, BP.IC; 24/03196-8 - Cloning, expression and purification of mitochondrial protein phosphatases, BP.TT; 23/13994-6 - Redox regulation and characterization of mitochondria protein phosphatase, BP.IC; + associated scholarships 22/14718-0 - In silico classification and structural characterization of proteins phosphatase from Aedes Aegypti mosquito, BP.IC; 23/02968-4 - Redox and structural regulation of Protein Tyrosine Phosphatase Mitochondrial 1 (PTPMT1), BP.MS; 22/02313-5 - Analysis of the ligands and the interaction network of the mitochondrial protein phosphatase PGAM5, BP.IC; 22/04064-2 - Mitochondrial protein phosphatases cloning, expression and purification, BP.TT; 21/10474-6 - Identification of mitochondrial DUSPs ligands through bioinformatics tools, BP.IC; 21/13213-9 - Redox regulation of mitochondrial protein phosphatases manganese-dependent and investigation of their network interactions, BP.IC; 20/10168-0 - Structural and functional characterization of mitochondrial protein phosphatases by redox metabolism and their role in cell biology, BP.JP - associated scholarships

Abstract

Protein phosphatases act in a coordinated way on cell signaling pathways that play a role in various physiological and pathological processes. These enzymes are found in several cellular compartments, such as cytosol and mitochondria, and the regulation of the activity of these enzymes is central to a better understanding of these processes. Although knowledge about mitochondrial protein phosphatases is very limited, it is known that some of these regulate cell metabolism, glucose homeostasis, insulin release and participate in the pathogenesis of numerous diseases. Cytoplasmic protein phosphatases are highly regulated by oxidants, however redox regulation of mitochondrial protein phosphatases is still unknown, moreover this organelle represents one of the major sites of cellular oxidant (ROS) production. Since cellular oxidants play an important role in modulating the enzyme activity and cellular processes, we postulate that the redox regulation of mitochondrial protein phosphatases should be unique and with direct implications for signaling, metabolism and cellular functions. Thus, this project aims to investigate the mechanism of redox regulation of mitochondrial protein phosphatases, through a functional and structural approach. As a result, we expected the identification of unique mechanisms of redox regulation of these enzymes. This will greatly contribute to a better understanding of the phosphatase inhibition by oxidation and the development of therapeutic tools using mitochondrial phosphatases as a target for the treatment of important human pathologies, such as diabetes and cancer. (AU)

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)

DURANS, ANDRESSA DA M.; NAPOLEAO-PEGO, PALOMA; REIS, FLAVIA C. G.; DIAS, EVANDRO R.; MACHADO, LUCIANA E. S. F.; LECHUGA, GUILHERME C.; JUNQUEIRA, ANGELA C. V.; DE-SIMONE, SALVATORE G.; PROVANCE JR, DAVID W.. Chagas Disease Diagnosis with Trypanosoma cruzi-Exclusive Epitopes in GFP. VACCINES, v. 12, n. 9, p. 17-pg., 2024-09-01. (19/02605-3, 20/10168-0)

CARVALHO, LAURA MACHADO LARA; BRANCO, ELISA VARELLA; SARAFIAN, RAQUEL DELGADO; KOBAYASHI, GERSON SHIGERU; DE ARAUJO, FABIANO TOFOLI; SOUZA, LUCAS SANTOS; MOREIRA, DANIELLE DE PAULA; HSIA, GABRIELLA SHIH PING; BERTOLLO, ENY MARIA GOLONI; BUCK, CECILIA BARBOSA; et al. Establishment of iPSC lines and zebrafish with loss-of-function AHDC1 variants: Models for Xia-Gibbs syndrome. Gene, v. 871, p. 10-pg., 2023-04-22. (20/03108-0, 20/04744-8, 13/08028-1, 20/10168-0, 18/08486-3, 19/02605-3)

NETTO, LUIS EDUARDO S.; MACHADO, LUCIANA ELENA S. F.. Preferential redox regulation of cysteine-based protein tyrosine phosphatases: structural and biochemical diversity. FEBS Journal, v. 289, n. 18, p. 25-pg., 2022-05-11. (13/07937-8, 19/02605-3, 20/10168-0)