Obtainment and functional evaluation of Trypanosoma cruzi mitochondrial complex v (F1FO-H+/ATPase)

• Grant number: 18/09634-6
• Support Opportunities: Research Grants - Visiting Researcher Grant - International
• Start date: July 16, 2018
• End date: July 29, 2018
• Field of knowledge: Biological Sciences - Parasitology - Protozoology of Parasites
• Principal Investigator: Ariel Mariano Silber
• Grantee: Ariel Mariano Silber
• Visiting researcher: Achim Schnaufer
• Visiting researcher institution: University of Edinburgh, Scotland
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 16/06034-2 - The biological role of amino acids and their metabolites in Trypanosoma cruzi, AP.TEM

Abstract

Trypanosomatids are deficient in some of the components of the Complex I of the respiratory chain. This limits the cell ability to re-oxidize NADH to keep an adequate ratio NAD+/NADH, which in turn is critical for a normal functionality of critical metabolic pathways, such as glycolysis or the oxidation of some amino acids. However, the functionality of the other complexes of the electron transfer chain is well documented, and the oxidative phosphorylation through the coupling of the respiratory chain to ATP synthesis through mitochondrial complex V (F1FO-ATP synthase) is well demonstrated. However, differently from what happens with complexes I to IV, little attention was given to complex V in Trypanosoma cruzi. Its study could be of relevance in the understanding of the parasite´s bioenergetics, since as shown in other phylogenetically related organisms, complex V could be involved in other functions differently from those expected. An example of this, is the fact that complex V is not involved in ATP synthesis in bloodstream forms of T. brucei. Instead, it is involved in avoiding the collapse of the mitochondrial inner membrane potential, hydrolyzing ATP to accomplish this function. In fact, some structural aspects of this complex seem to be specifically adapted to this function. This proposal is framed in a starting collaboration with Prof. Achim Schnaufer, probably the most experienced researcher in F1FO-ATP synthases of trypanossomatids. Prof. Schanufer will come to our laboratory (if the proposal is approved) in order to help us to establish one of the most relevant methods to initiate this kind of study in T. cruzi. (AU)