The unicellular parasite Trypanosoma brucei has a digenetic life cycle that alternates between a mammalian host and an insect vector. During programmed development, this extracellular parasite encounters strikingly different environments that determine its energy metabolism. Functioning as a bioenergetic, biosynthetic, and signaling center, the single mitochondrion of T. brucei is drastically remodeled to support the dynamic cellular demands of the parasite. This manuscript will provide an up-to-date overview of how the distinct T. brucei developmental stages differ in their mitochondrial metabolic and bioenergetic pathways, with a focus on the electron transport chain, proline oxidation, TCA cycle, acetate production, and ATP generation. Although mitochondrial metabolic rewiring has always been simply viewed as a consequence of the differentiation process, the possibility that certain mitochondrial activities reinforce parasite differentiation will be explored.
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http://dx.doi.org/10.1111/jeu.12911 | DOI Listing |
Nat Struct Mol Biol
January 2025
Laboratory of Regulation of Gene Expression, Institute of Microbiology, Czech Academy of Sciences, Prague, Czech Republic.
Transfer RNAs (tRNAs) serve as a dictionary for the ribosome translating the genetic message from mRNA into a polypeptide chain. In addition to this canonical role, tRNAs are involved in other processes such as programmed stop codon readthrough (SC-RT). There, tRNAs with near-cognate anticodons to stop codons must outcompete release factors and incorporate into the ribosomal decoding center to prevent termination and allow translation to continue.
View Article and Find Full Text PDFMicrotubule-severing enzymes play essential roles in regulating diverse cellular processes, including mitosis and cytokinesis, by modulating microtubule dynamics. In the early branching protozoan parasite , microtubule-severing enzymes are involved in cytokinesis and flagellum length control during different life cycle stages, but none of them have been found to regulate mitosis in any life cycle form. Here, we report the biochemical and functional characterization of the microtubule-severing enzyme spastin in the procyclic form of .
View Article and Find Full Text PDFMicrobiol Spectr
January 2025
Department of Molecular and Comparative Pathobiology, Johns Hopkins University, School of Medicine, Baltimore, Maryland, USA.
Unlabelled: is a protozoan parasite that causes human and animal African trypanosomiases (HAT and AAT). Cardiac symptoms are commonly reported in HAT patients, and intracardiac parasites with accompanying myocarditis have been observed in both natural hosts and animal models of infection. Despite the importance of as a cause of cardiac dysfunction and the dramatic socioeconomic impact of African trypanosomiases in sub-Saharan Africa, there are currently no reproducible murine models of associated cardiomyopathy.
View Article and Find Full Text PDFClin Microbiol Rev
January 2025
School of Infection and Immunity, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom.
SUMMARYPrior to 2019, when the orally available drug fexinidazole began its clinical use, the treatment of human African trypanosomiasis (HAT) was complex and unsatisfactory for many reasons. Two sub-species of the parasite are responsible for HAT, namely the rhodesiense form found in East and Southern Africa and the gambiense form found in Central and West Africa. Diseases caused by both forms manifest in two stages: stage 1 before and stage 2 after central nervous system involvement.
View Article and Find Full Text PDFMolecules
December 2024
Departamento de Bioquímica y Farmacología Molecular, Instituto de Parasitología y Biomedicina López Neyra, CSIC, PTS Granada, Avenida del Conocimiento 17, 18016 Armilla, Spain.
G-quadruplexes (G4s) are non-canonical secondary structures that play a crucial role in the regulation of genetic expression. This study explores the interaction between G4s and a small family of oligostyrylbenzene (OSB) derivatives, characterized by tris(styryl)benzene and tetrastyrylbenzene backbones, functionalized with either trimethylammonium or 1-methylpyridinium groups. Initially identified as DNA ligands, these OSB derivatives have now been recognized as potent G4 binders, surpassing in binding affinity commercially available ligands such as pyridostatin and displaying good selectivity for G4s over duplex DNA.
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