Determination of the interatome, funcional caracterization and other Trypanosoma cruzi mitochondrial tryparedoxin peroxidase intracellular localizations

• Grant number: 11/19872-2
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: February 01, 2012
• End date: January 31, 2015
• Field of knowledge: Biological Sciences - Biochemistry
• Principal Investigator: Fernanda Ramos Gadelha
• Grantee: Eduardo de Figueiredo Peloso
• Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil

Abstract

Among the proteins of the Trypanosoma cruzi antioxidant system, unique in trypanosomatids, cytosolic and mitochondrial tryparedoxin peroxidases (TcCPx and TcMPx, respectively) have an important role in parasite's virulence and viability. The cytosolic antioxidant system has been elucidated, but its main components, like tryparedoxin or trypanothione, have not been identified in the mitochondrion. In this sense, how the mitochondrial system works is still a matter of debate. Bioinformatics analysis, immunolocalization and bioenergetic experiments carried out by our group suggest its localization in the mitochondrion membrane and in the cytosol, which would allow it to interact with the cytosolic trypanothione-dependent system. Additionally, a TcMPx larger band (28kDa) was detected by immunoblotting being more expressed under oxidative stress conditions. In this sense, this project aim to determine TcMPx exact intracellular location, its interatome, specify which domain, N- or C-terminal is facing the citosol, possible migration in the cell under oxidative stress and establish the 28kDa protein sequence. The results will provide valuable information regarding the strategies used by the parasite to detoxify hydroperoxides dependent on TcMPx and its possible role in mitochondrial bioenergetics. So, new targets will be identified that could lead to the development of a more specific therapy and as so, less toxic to the vertebrate host.

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)

PELOSO, E. F.; DIAS, L.; QUEIROZ, R. M. L.; LEME, A. F. P. PAES; PEREIRA, C. N.; CARNIELLI, C. M.; WERNECK, C. C.; SOUSA, M. V.; RICART, C. A. O.; GADELHA, F. R.. Trypanosoma cruzi mitochondrial tryparedoxin peroxidase is located throughout the cell and its pull down provides one step towards the understanding of its mechanism of action. BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS, v. 1864, n. 1, p. 1-10, JAN 2016. (11/20084-9, 11/19872-2)

DIAS, L.; PELOSO, E. F.; LEME, A. F. P.; CARNIELLI, C. M.; PEREIRA, C. N.; WERNECK, C. C.; GUERRERO, S.; GADELHA, F. R.. Trypanosoma cruzi tryparedoxin II interacts with different peroxiredoxins under physiological and oxidative stress conditions. Experimental Parasitology, v. 184, p. 1-10, JAN 2018. (11/20084-9, 11/19872-2)