ArticleCell & bioscience2016
Universal minicircle sequence binding protein of Leishmania donovani regulates pathogenicity by controlling expression of cytochrome-b.
Article in Cell & bioscience, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. Cited by 10 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
10 citing papers in PubMed, 16 citations in OpenAlex.
- UMSBP2 is chromatin remodeler that functions in regulation of gene expression and suppression of antigenic variation in trypanosomes.Nucleic acids research · 2023Article
- Aberrant Expression of Mitochondrial SAM Transporter SLC25A26 Impairs Oocyte Maturation and Early Development in Mice.Oxidative medicine and cellular longevity · 2022Article
- The Complete Mitochondrial DNA ofFrontiers in cellular and infection microbiology · 2021Article
- Molecular and Functional Characteristics of DNA Polymerase Beta-Like Enzymes From Trypanosomatids.Frontiers in cellular and infection microbiology · 2021Review
- Redox Balance Keepers and Possible Cell Functions Managed by Redox Homeostasis inFrontiers in cellular and infection microbiology · 2019Review
- Trypanothione synthetase confers growth, survival advantage and resistance to anti-protozoal drugs in Trypanosoma cruzi.Free radical biology & medicine · 2019Article
- Trypanosoma brucei UMSBP2 is a single-stranded telomeric DNA binding protein essential for chromosome end protection.Nucleic acids research · 2018Article
- Article
- A comparative molecular and 3-dimensional structural investigation into cross-continental and novel avian Trypanosoma spp. in Australia.Parasites & vectors · 2017Article
- Comprehensive Identification of mRNA-Binding Proteins of Leishmania donovani by Interactome Capture.PloS one · 2017Article
Corrections and comments
- Expression of concern · 2022-02-15Concerns/Issues about Data · Updated to Retraction · · see also: https://pubpeer.com/publications/5B2FF1135DF5EF1F5D5A8D39544524
- Retraction · 2022-08-22Duplication of/in Image · Original Data and/or Images not Provided and/or not Available · Upgrade/Update of Prior Notice(s) · · see also: https://pubpeer.com/publications/5B2FF1135DF5EF1F5D5A8D39544524
- Retracted
Authors and funding
14 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundLeishmania contains a concatenated mitochondrial DNA, kDNA. Universal minicircle sequence binding protein (UMSBP), a mitochondrial protein, initiates kDNA replication by binding with a conserved universal minicircle sequence (UMS) of kDNA. Here, we describe first time in L. donovani the regulation of DNA binding activity of UMSBP and the role of UMSBP in virulence.
methodsInsilco and EMSA study were performed to show UMS-binding activity of UMSBP. Tryparedoxin(TXN)-tryparedoxin peroxidase(TXNPx) assay as well as co-overexpression of cytochrome-b5 reductase-like protein (CBRL) and tryparedoxin in L. donovani were done to know the regulation of DNA binding activity of UMSBP. Knockout and episomal-expression constructs of UMSBP were transfected in L. donovani. The cell viability assay and immunofluorescence study to know the status of kDNA were performed. Macrophages were infected with transfected parasites. mRNA level of cytochrome b, activity of complex-III, intracellular ATP level of both transfected promastigotes and amastigotes as well as ROS concentration and the level of apoptosis of transfected promastigotes were measured. Level of oxidative phosphorylation of both transfected and un-transfected amastigotes were compared. Burden of transfected amastigotes in both macrophages and BALB/c mice were measured.
resultsL. donovani UMSBP is capable of binding with UMS, regulated by redox through mitochondrial enzymes, TXN, TXNPx and CBRL. Depletion of UMSBP (LdU(-/-)) caused kDNA loss, which decreased cytochrome-b expression [component of complex-III of electron transport chain (ETC)] and leads to the disruption of complex-III activity, decreased ATP generation, increased ROS level and promastigotes exhibited apoptosis like death. Interestingly, single knockout of UMSBP (LdU(-/+)) has no effect on promastigotes survival. However, single knockout in intracellular amastigotes demonstrate loss of mRNA level of cytochrome-b, disruption in the activity of complex-III and reduced production of ATP in amastigotes than wild type. This process interfere with the oxidative-phosphorylation and thereby completely inhibit the intracellular proliferation of LdU(-/+) amastigotes in human macrophages and in BALB/c mice. Amastigotes proliferation was restored as wild type after episomal expression of LdUMSBP in LdU(-/+) parasites (LdU(-/+)AB).
conclusionThe LdUMSBP regulates leishmanial mitochondrial respiration and pathogenesis. So, LdUMSBP may be an attractive target for rational drug designing and LdU(-/+) parasites could be considered as a live attenuated vaccine candidate against visceral leishmaniasis.
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