The RNA Import Complex (RIC) is a multi-subunit protein complex from the mitochondria of the kinetoplastid protozoon Leishmania tropica that induces transport of tRNA across natural and artificial membranes. Leishmania, Trypanosoma and related genera of the order Kinetoplastidae are early diverging, atypical eukaryotes with unique RNA metabolic pathways, including the import of nucleus-encoded tRNAs into the mitochondrion to complement the deletion of all organelle-encoded tRNA genes. Biochemical and genetic studies of RIC are contributing to greater understanding of the mechanism of import. Additionally, RIC was shown to act as an efficient delivery vehicle for tRNA and other small RNAs into mitochondria within intact mammalian cells, indicating its applicability to the management of diseases caused by mitochondrial mutations.
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http://dx.doi.org/10.1016/j.biocel.2007.10.025 | DOI Listing |
Exp Parasitol
January 2025
Natural Products Chemistry Laboratory, State University of Ceará, Fortaleza, Brazil. Electronic address:
The current treatment of leishmaniasis is confronted with significant challenges, including limited efficacy, adverse effects, and parasite resistance to drugs. The search for alternative therapeutic options, including the utilisation of natural products, has demonstrated considerable promise. In this study, the antileishmanial activity of the flavonoid hesperetin against Leishmania donovani, the causative agent of visceral leishmaniasis, was reported for the first time.
View Article and Find Full Text PDFPLoS Negl Trop Dis
January 2025
Instituto Gonçalo Moniz, Fundação Oswaldo Cruz, Salvador, Brazil.
Macrophages represent a fundamental component of the innate immune system that play a critical role in detecting and responding to pathogens as well as danger signals. Leishmania spp. infections lead to a notable alteration in macrophage metabolism, whereby infected cells display heightened energy metabolism that is linked to the integrity of host mitochondria.
View Article and Find Full Text PDFParasit Vectors
January 2025
Center of Excellence in Veterinary Parasitology, Department of Pathology, Faculty of Veterinary Science, Chulalongkorn University, Bangkok, 10330, Thailand.
Background: The subfamily Phlebotominae comprises 1028 species of sand fly, of which only 90 are recognized as vectors of pathogenic agents such as Trypanosoma, Leishmania, and Bartonella. In Thailand, leishmaniasis-a sand fly-borne disease-is currently endemic, with 36 documented sand fly species. However, many cryptic species likely remain unidentified.
View Article and Find Full Text PDFInt J Parasitol Drugs Drug Resist
December 2024
São Paulo State University (Unesp), School of Pharmaceutical Sciences, Araraquara, São Paulo, Brazil. Electronic address:
Leishmaniasis is a neglected disease that remains with a limited number of drugs available for chemotherapy and has an increased drug resistance that affects treatment outcomes. Metal-based drugs such as cyclopalladated complex [Pd(dmba)(μ-N)] (CP2), a Leishmania topoisomerase IB inhibitor involved in calcium dysregulation and mitochondrial dysfunction of the parasite, had been an alternative to outline the appearance of chemoresistance. To identify new molecular targets and point out possible resistance mechanisms, a CP2-resistant Leishmania amazonensis (LaR) was selected by stepwise exposure to increasing drug pressure until a line capable of growth in 13.
View Article and Find Full Text PDFEur J Med Chem
February 2025
Laboratory of Planning in Medicinal Chemistry, Department of Pharmaceutical Sciences, Center for Health Sciences, Federal University of Pernambuco, 50740-535, Recife, PE, Brazil. Electronic address:
Trypanosomatidae diseases, such as Chagas disease and leishmaniasis, are caused by protozoan parasites of the Trypanosomatidae family, namely Trypanosoma cruzi and Leishmania species, respectively. There is an urgent need for new therapies. Both pyridine and thiazole rings are recognized as important scaffolds in medicinal chemistry.
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