scholarly journals Characterization and role of the 3-methylglutaconyl coenzyme A hidratase in Trypanosoma brucei

2017 ◽  
Vol 214 ◽  
pp. 36-46 ◽  
Author(s):  
Mariana Leão de Lima Stein ◽  
Marcelo Yudi Icimoto ◽  
Erica Valadares de Castro Levatti ◽  
Vitor Oliveira ◽  
Anita Hilda Straus ◽  
...  
2014 ◽  
Vol 2014 ◽  
pp. 1-14 ◽  
Author(s):  
Rubem Figueiredo Sadok Menna-Barreto ◽  
Solange Lisboa de Castro

The pathogenic trypanosomatidsTrypanosoma brucei,Trypanosoma cruzi, andLeishmaniaspp. are the causative agents of African trypanosomiasis, Chagas disease, and leishmaniasis, respectively. These diseases are considered to be neglected tropical illnesses that persist under conditions of poverty and are concentrated in impoverished populations in the developing world. Novel efficient and nontoxic drugs are urgently needed as substitutes for the currently limited chemotherapy. Trypanosomatids display a single mitochondrion with several peculiar features, such as the presence of different energetic and antioxidant enzymes and a specific arrangement of mitochondrial DNA (kinetoplast DNA). Due to mitochondrial differences between mammals and trypanosomatids, this organelle is an excellent candidate for drug intervention. Additionally, during trypanosomatids’ life cycle, the shape and functional plasticity of their single mitochondrion undergo profound alterations, reflecting adaptation to different environments. In an uncoupling situation, the organelle produces high amounts of reactive oxygen species. However, these species role in parasite biology is still controversial, involving parasite death, cell signalling, or even proliferation. Novel perspectives on trypanosomatid-targeting chemotherapy could be developed based on better comprehension of mitochondrial oxidative regulation processes.


2020 ◽  
Vol 3 (1) ◽  
Author(s):  
Chu-Ya Wu ◽  
I-Chen Hu ◽  
Yi-Chen Yang ◽  
Wei-Cheng Ding ◽  
Chih-Hsuan Lai ◽  
...  

Author(s):  
Kirsten J. Meyer ◽  
Theresa A. Shapiro

Trypanosoma brucei subspecies cause African sleeping sickness in humans, an infection that is commonly fatal if not treated, and available therapies are limited. Previous studies have shown that heat shock protein 90 (Hsp90) inhibitors have potent and vivid activity against bloodstream form trypanosomes. Hsp90s are phylogenetically conserved and essential catalysts that function at the crux of cell biology, where they ensure the proper folding of proteins and their assembly into multicomponent complexes. To assess the specificity of Hsp90 inhibitors and further define the role of Hsp90s in African trypanosomes, we used RNAi to knockdown cytosolic and mitochondrial Hsp90s (HSP83 and HSP84, respectively). Loss of either protein led to cell death but the phenotypes were distinctly different. Depletion of cytosolic HSP83 closely mimicked the consequences of chemically depleting Hsp90 activity with inhibitor 17-AAG. In these cells cytokinesis was severely disrupted and segregation of the kinetoplast (the massive mitochondrial DNA structure unique to this family of eukaryotic pathogens) was impaired, leading to cells with abnormal kDNA structures. Quite differently, knockdown of mitochondrial HSP84 did not impair cytokinesis but halted the initiation of new kDNA synthesis, generating cells without kDNA. These findings highlight the central role for Hsp90s in chaperoning cell cycle regulators in trypanosomes, reveal their unique function in kinetoplast replication, and reinforce their specificity and value as drug targets.


2005 ◽  
Vol 52 (2) ◽  
pp. 35S-38S
Author(s):  
O. SMID ◽  
E. VONDRUSKOVA ◽  
V. VILIMOVA ◽  
R. SUT'AK ◽  
J. LUKE ◽  
...  

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