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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Higher expression of proline dehydrogenase altered mitochondrial function and increased Trypanosoma cruzi differentiation in vitro and in the insect vector

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Author(s):
Mantilla, Brian S. [1, 2] ; Paes-Vieira, Lisvane [2, 3] ; Dias, Felipe de Almeida [3] ; Calderano, Simone G. [4] ; Elias, Maria Carolina [4] ; Cosentino-Gomes, Daniela [3, 5] ; Oliveira, Pedro L. [3] ; Meyer-Fernandes, Jose Roberto [3] ; Silber, Ariel M. [2]
Total Authors: 9
Affiliation:
[1] Univ Durham, Dept Biosci, Durham DH1 3LE - England
[2] Univ Sao Paulo, Inst Biomed Sci, Dept Parasitol, Lab Biochem Tryps LaBTryps, Sao Paulo, SP - Brazil
[3] Univ Fed Rio de Janeiro, Inst Bioquim Med Leopoldo Meis, Rio De Janeiro, RJ - Brazil
[4] Inst Butantan, Ctr Toxines Immune Response & Cell Signallig, Lab Ciclo Celular, Sao Paulo - Brazil
[5] Univ Fed Rural Rio de Janeiro, Inst Quim, Dept Bioquim, Seropedica, RJ - Brazil
Total Affiliations: 5
Document type: Journal article
Source: Biochemical Journal; v. 478, n. 21, p. 3891-3903, NOV 2021.
Web of Science Citations: 0
Abstract

The pathogenic protist Trypanosoma cruzi uses kissing bugs as invertebrate hosts that vectorize the infection among mammals. This parasite oxidizes proline to glutamate through two enzymatic steps and one nonenzymatic step. In insect vectors, T. cruzi differentiates from a noninfective replicating form to nonproliferative infective forms. Proline sustains this differentiation, but to date, a link between proline metabolism and differentiation has not been established. In T. cruzi, the enzymatic steps of the proline-glutamate oxidation pathway are catalyzed exclusively by the mitochondrial enzymes proline dehydrogenase {[}TcPRODH, EC: 1.5.5.2] and Delta 1-pyrroline-5-carboxylate dehydrogenase {[}TcP5CDH, EC: 1.2.1.88]. Both enzymatic steps produce reducing equivalents that are able to directly feed the mitochondrial electron transport chain (ETC) and thus produce ATP. In this study, we demonstrate the contribution of each enzyme of the proline-glutamate pathway to ATP production. In addition, we show that parasites overexpressing these enzymes produce increased levels of H2O2, but only those overexpressing TcP5CDH produce increased levels of superoxide anion. We show that parasites overexpressing TcPRODH, but not parasites overexpressing TcP5CDH, exhibit a higher rate of differentiation into metacyclic trypomastigotes in vitro. Finally, insect hosts infected with parasites overexpressing TcPRODH showed a diminished parasitic load but a higher percent of metacyclic trypomastigotes, when compared with controls. Our data show that parasites overexpressing both, PRODH and P5CDH had increased mitochondrial functions that orchestrated different oxygen signaling, resulting in different outcomes in relation to the efficiency of parasitic differentiation in the invertebrate host. (AU)

FAPESP's process: 16/06034-2 - The biological role of amino acids and their metabolites in Trypanosoma cruzi
Grantee:Ariel Mariano Silber
Support Opportunities: Research Projects - Thematic Grants
FAPESP's process: 18/14432-3 - A network for an integrative biology in neglected diseases: bridging epigenetics, metabolism and cell cycle in pathogenic trypanosomatids
Grantee:Ariel Mariano Silber
Support Opportunities: Research Projects - Thematic Grants