期刊
BIOCHEMICAL JOURNAL
卷 478, 期 21, 页码 3891-3903出版社
PORTLAND PRESS LTD
DOI: 10.1042/BCJ20210428
关键词
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资金
- Fundacao de Amparo a Pesquisa do Estado de Sao Paulo [2016/06034-2, 2018/14432-3]
- Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq) [308351/2013-4, 404769/2018-7]
- Research Council United Kingdom [MR/P027989/1]
The pathogenic protist Trypanosoma cruzi utilizes kissing bugs as invertebrate hosts to vectorize infection among mammals. Through the proline-glutamate oxidation pathway, mitochondrial enzymes play a crucial role in differentiation and energy production in the parasite. Overexpression of these enzymes leads to increased mitochondrial functions and different oxygen signaling, influencing parasitic differentiation efficiency in the invertebrate host.
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.
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