L-Glutamine uptake is developmentally regulated and is involved in metacyclogenesis in Trypanosoma cruzi

Autor(es)

Damasceno, Flavia S. ^[1] ; Barison, Maria Julia ^[1] ; Crispim, Marcell ^[1] ; Souza, Rodolpho O. O. ^[1] ; Marchese, Leticia ^[1] ; Silber, Ariel M. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Inst Biomed Sci, Dept Parasitol, Lab Biochem Tryps LaBTryps, Av Prof Lineu Prestes 1374, BR-05508000 Sao Paulo, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Molecular and Biochemical Parasitology; v. 224, p. 17-25, SEP 15 2018.
• Citações Web of Science: 0

Resumo

Trypanosoma cruzi, the aetiological agent of Chagas disease, can obtain L-glutamine (Gln) through the enzyme glutamine synthetase (GS) using glutamate (Glu) and ammonia as substrates. In this work, we show additional non-canonical roles for this amino acid: its involvement in ATP maintenance and parasite survival under severe metabolic stress conditions and its participation in the differentiation process occurring in the insect vector (metacyclogenesis). These roles are dependent on the supply of Gln from an extracellular source. We show that T. cruzi incorporates Gln through a saturable and specific transport system, which results in unusual stability at elevated temperatures. The activity was moderately higher at pH values between 6 and 7 and was sensitive to the dissipation of the H+ gradient at the plasma membrane. When analysed in the different life cycle stages, we found that Gln transport is developmentally regulated. In fact, Gln uptake and GS activity seem to be finely regulated at most stages: when GS activity is increased, transport is decreased and vice versa, with the exception of trypomastigotes, where both sources of Gln are diminished. This metabolic adaptation reflects the relevance of Gln in T. cruzi biology and the plasticity of these parasites to adjust their metabolism to changing environments. (AU)

• Processo FAPESP: 16/06034-2 - O papel biológico de aminoácidos e seus metabólitos derivados em Trypanosoma cruzi
• Beneficiário: Ariel Mariano Silber
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 17/16553-0 - O papel das isoformas mitocondrial e glicossomal da fumarato redutase na bioenergética de Trypanosoma cruzi
• Beneficiário: Ariel Mariano Silber
• Modalidade de apoio: Auxílio à Pesquisa - Pesquisador Visitante - Internacional