Functional study of MICU1 and MICU2 proteins involved in Trypanosoma Cruzi calcium signaling

• Grant number: 15/25709-8
• Support type: Scholarships in Brazil - Master
• Effective date (Start): April 01, 2016
• Effective date (End): February 28, 2018
• Field of knowledge: Biological Sciences - Biochemistry
• Principal Investigator: Aníbal Eugênio Vercesi
• Grantee: Mayara Santos Bertolini
• Home Institution: Faculdade de Ciências Médicas (FCM). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil

Abstract

Trypanosoma cruzi is the etiologic agent of Chagas disease, a disorder affecting thousands of people, for which an effective treatment is not available yet. This parasite exhibits several stages, where calcium signaling plays an important role in the adaptation to environmental changes encountered during its life cycle. In trypanosomatids, among other functions, calcium signaling is important for host cell invasion, differentiation, osmoregulation, cell death and flagellar function. The influx of calcium into the mitochondria, which is important for intracellular calcium homeostasis, occurs through a mitochondrial calcium uniporter complex (MCUC). This complex consists of several components, including two regulatory proteins named mitochondrial calcium uptake 1 and 2 (MICU1 and MICU2), that inhibit the Mitochondrial Calcium Uniporter activity at low calcium concentration, preventing mitochondrial overload and stimulating MCU activity at high cytosolic calcium concentration. Our research group showed several biological aspects of MCU in T. brucei and we are currently studying MCU in T. cruzi, however both regulations are still not well known. In this project, we propose to evaluate the effect of MICU2 and MICU2 overexpression and knockout in Trypanosoma cruzi epimastigotes, suggesting that it will modify the MCUC sensitivity to citosolic calcium concentrations. The relevance of this study relies on the need of elucidating the cellular mechanisms involving calcium homeostasis in this parasite, while it could also provide important information to enable the future development of more effective drugs for the treatment of Chagas disease.

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)

CHIURILLO, MIGUEL A.; LANDER, NOELIA; BERTOLINI, MAYARA S.; VERCESI, ANIBAL E.; DOCAMPO, ROBERTO. Functional analysis and importance for host cell infection of the Ca2+-conducting subunits of the mitochondrial calcium uniporter of Trypanosoma cruzi. MOLECULAR BIOLOGY OF THE CELL, v. 30, n. 14, p. 1676-1690, JUL 1 2019. Web of Science Citations: 1.

BERTOLINI, MAYARA S.; CHIURILLO, MIGUEL A.; LANDER, NOELIA; VERCESI, ANIBAL E.; DOCAMPO, ROBERTO. MICU1 and MICU2 Play an Essential Role in Mitochondrial Ca2+ Uptake, Growth, and Infectivity of the Human Pathogen Trypanosoma cruzi. MBIO, v. 10, n. 3 MAY-JUN 2019. Web of Science Citations: 1.

LANDER, NOELIA; CHIURILLO, MIGUEL A.; BERTOLINI, MAYARA S.; DOCAMPO, ROBERTO; VERCESI, ANIBAL E. The mitochondrial calcium uniporter complex in trypanosomes. Cell Biology International, v. 42, n. 6, SI, p. 656-663, JUN 2018. Web of Science Citations: 2.

CHIURILLO, MIGUEL A.; LANDER, NOELIA; BERTOLINI, MAYARA S.; STOREY, MELISSA; VERCESI, ANIBAL E.; DOCAMPO, ROBERTO. Different Roles of Mitochondrial Calcium Uniporter Complex Subunits in Growth and Infectivity of Trypanosoma cruzi. MBIO, v. 8, n. 3 MAY-JUN 2017. Web of Science Citations: 23.

Academic Publications

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

BERTOLINI, Mayara Santos. Functional study of MICU1 and MICU2 proteins in calcium signaling of "Trypanosoma cruzi". 2018. Master's Dissertation.