Iron Uptake Controls Trypanosoma cruzi Metabolic Shift and Cell Proliferation

• Published in: Antioxidants 2023-04, Vol.12 (5), p.984
• Main Authors: Dick, Claudia F, Alcantara, Carolina L, Carvalho-Kelly, Luiz F, Lacerda-Abreu, Marco Antonio, Cunha-E-Silva, Narcisa L, Meyer-Fernandes, José R, Vieyra, Adalberto
• Format: Article
• Language: English
• Subjects: ATP synthesis; Bioluminescence; Cell culture; Cell growth; Cell proliferation; Chagas disease; Cytochrome c; Cytometry; Endocytosis; Epimastigotes; Glucokinase; Glyceraldehyde-3-phosphate dehydrogenase; Glycolysis; growth and differentiation; Hemoglobin; Hydrogen peroxide; Hypotheses; Intracellular; Life cycles; Membrane potential; Metabolism; Mitochondria; mitochondrial function; Organelles; Oxidative stress; Oxidoreductase; Oxygen consumption; parasite lipid content; parasite oxidative stress; Parasites; Propagation; Protein kinase A; Proteins; Protozoa; Transmission electron microscopy; Trypanosoma cruzi; trypanosomatids; Western blotting
• ISSN: 2076-3921; 2076-3921
• DOI: 10.3390/antiox12050984

(1) Background: Ionic transport in is the object of intense studies. expresses a Fe-reductase (TcFR) and a Fe transporter (TcIT). We investigated the effect of Fe depletion and Fe supplementation on different structures and functions of epimastigotes in culture. (2) Methods: We investigated growth and metacyclogenesis, variations of intracellular Fe, endocytosis of transferrin, hemoglobin, and albumin by cell cytometry, structural changes of organelles by transmission electron microscopy, O consumption by oximetry, mitochondrial membrane potential measuring JC-1 fluorescence at different wavelengths, intracellular ATP by bioluminescence, succinate-cytochrome c oxidoreductase following reduction of ferricytochrome c, production of H O following oxidation of the Amplex red probe, superoxide dismutase (SOD) activity following the reduction of nitroblue tetrazolium, expression of SOD, elements of the protein kinase A (PKA) signaling, TcFR and TcIT by quantitative PCR, PKA activity by luminescence, glyceraldehyde-3-phosphate dehydrogenase abundance and activity by Western blotting and NAD reduction, and glucokinase activity recording NADP reduction. (3) Results: Fe depletion increased oxidative stress, inhibited mitochondrial function and ATP formation, increased lipid accumulation in the reservosomes, and inhibited differentiation toward trypomastigotes, with the simultaneous metabolic shift from respiration to glycolysis. (4) Conclusion: The processes modulated for ionic Fe provide energy for the life cycle and the propagation of Chagas disease.