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 Δ1-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.
-
Cover Image
Cover Image
The dimeric reaction centre light-harvesting 1 (RC-LH1) core complex of Rhodobacter sphaeroides converts absorbed light energy to a charge separation, and then it reduces a quinone electron and proton acceptor to a quinol. In this issue, Qian and colleagues (pp. 3923–3937) investigate the dimerisation interface between two RC-LH1 monomers, and determine the cryogenic electron microscopy structure of the dimeric complex at 2.9 Å resolution. The cover image shows the role of PufX in imposing a bent conformation on the RC-LH1 dimer complex. The top view is of the cytoplasmic side of the membrane and the bottom view is in the plane of the membrane. Image courtesy of C. Neil Hunter.
Higher expression of proline dehydrogenase altered mitochondrial function and increased Trypanosoma cruzi differentiation in vitro and in the insect vector
Brian S. Mantilla, Lisvane Paes-Vieira, Felipe de Almeida Dias, Simone G. Calderano, Maria Carolina Elias, Daniela Cosentino-Gomes, Pedro L. Oliveira, José Roberto Meyer-Fernandes, Ariel M. Silber; Higher expression of proline dehydrogenase altered mitochondrial function and increased Trypanosoma cruzi differentiation in vitro and in the insect vector. Biochem J 12 November 2021; 478 (21): 3891–3903. doi: https://doi.org/10.1042/BCJ20210428
Download citation file:
Sign in
Sign in to your personal account
Captcha Validation Error. Please try again.