ArticlePloS one2013
Proline dehydrogenase regulates redox state and respiratory metabolism in Trypanosoma cruzi.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 81 citations in OpenAlex.
- High and Selective TrypanocidalMicroorganisms · 2026Article
- Proline dehydrogenase, a rate-limiting catabolic enzyme, affecting the growth and pathogenicity of Toxoplasma gondii tachyzoites by regulating the proline metabolism and mitochondrial function of the parasite.Parasites & vectors · 2025Article
- Energy metabolism inmBio · 2025Review
- The role of l-serine and l-threonine in the energy metabolism and nutritional stress response ofmSphere · 2025Article
- Knocking out histidine ammonia-lyase by using CRISPR-Cas9 abolishes histidine role in the bioenergetics and the life cycle ofMicrobial cell (Graz, Austria) · 2025Article
- Branched-chain amino acids modulate the proteomic profile of Trypanosoma cruzi metacyclogenesis induced by proline.PLoS neglected tropical diseases · 2024Article
- Article
- Autophagy in protists and their hosts: When, how and why?Autophagy reports · 2023Article
- Expanded Proteomic Survey of the Human Parasite Leishmania major Focusing on Changes in Null Mutants of the Golgi GDP-Mannose/Fucose/Arabinopyranose TransporterMicrobiology spectrum · 2022Article
- Fatty acid oxidation participates in resistance to nutrient-depleted environments in the insect stages of Trypanosoma cruzi.PLoS pathogens · 2021Article
- Biological and Molecular Effects ofFrontiers in cellular and infection microbiology · 2021Article
- Transcriptional remodeling during metacyclogenesis inVirulence · 2020Article
- Genome-scale metabolic models highlight stage-specific differences in essential metabolic pathways in Trypanosoma cruzi.PLoS neglected tropical diseases · 2020Article
- Glutamine Analogues Impair Cell Proliferation, the Intracellular Cycle and Metacyclogenesis inMolecules (Basel, Switzerland) · 2020Article
- Measurement of Energy States of the Trypanosomatid Mitochondrion.Methods in molecular biology (Clifton, N.J.) · 2020Article
- Targeting L-Proline Uptake as New Strategy for Anti-chagas Drug Development.Frontiers in chemistry · 2020Article
- Diminished Prolinemia in Chronic Chagasic Patients: A New Clue for Disease Pathology?Molecules (Basel, Switzerland) · 2019Article
- Role of Proline in Pathogen and Host Interactions.Antioxidants & redox signaling · 2019Review
- RNA-Seq Revealed Expression of Many Novel Genes Associated WithFrontiers in cellular and infection microbiology · 2019Article
- Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Over the past three decades, L-proline has become recognized as an important metabolite for trypanosomatids. It is involved in a number of key processes, including energy metabolism, resistance to oxidative and nutritional stress and osmoregulation. In addition, this amino acid supports critical parasite life cycle processes by acting as an energy source, thus enabling host-cell invasion by the parasite and subsequent parasite differentiation. In this paper, we demonstrate that L-proline is oxidized to Δ(1)-pyrroline-5-carboxylate (P5C) by the enzyme proline dehydrogenase (TcPRODH, E.C. 1.5.99.8) localized in Trypanosoma cruzi mitochondria. When expressed in its active form in Escherichia coli, TcPRODH exhibits a Km of 16.58±1.69 µM and a Vmax of 66±2 nmol/min mg. Furthermore, we demonstrate that TcPRODH is a FAD-dependent dimeric state protein. TcPRODH mRNA and protein expression are strongly upregulated in the intracellular epimastigote, a stage which requires an external supply of proline. In addition, when Saccharomyces cerevisiae null mutants for this gene (PUT1) were complemented with the TcPRODH gene, diminished free intracellular proline levels and an enhanced sensitivity to oxidative stress in comparison to the null mutant were observed, supporting the hypothesis that free proline accumulation constitutes a defense against oxidative imbalance. Finally, we show that proline oxidation increases cytochrome c oxidase activity in mitochondrial vesicles. Overall, these results demonstrate that TcPRODH is involved in proline-dependant cytoprotection during periods of oxidative imbalance and also shed light on the participation of proline in energy metabolism, which drives critical processes of the T. cruzi life cycle.
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