ArticleMolecular biology of the cell2004
Mitochondrial localization of the mevalonate pathway enzyme 3-Hydroxy-3-methyl-glutaryl-CoA reductase in the Trypanosomatidae.
Article in Molecular biology of the cell, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
21 citing papers in PubMed, 48 citations in OpenAlex.
- The mevalonate and methylerythritol phosphate pathways as therapeutic targets in protozoan parasites: from moonlighting enzymes to metabolic plasticity.Cell communication and signaling : CCS · 2026Review
- Perturbations in mitochondrial metabolism associated with defective cardiolipin biosynthesis: AnbioRxiv : the preprint server for biology · 2024Article
- Genomics of Preaxostyla Flagellates Illuminates the Path Towards the Loss of Mitochondria.PLoS genetics · 2023Article
- Antiplasmodial, Trypanocidal, and GenotoxicityPharmaceuticals (Basel, Switzerland) · 2023Article
- Navigating drug repurposing for Chagas disease: advances, challenges, and opportunities.Frontiers in pharmacology · 2023Review
- The expression pattern, subcellular localization and function of three sterol 14α-demethylases inFrontiers in genetics · 2023Article
- Validation of Plasmodium falciparum dUTPase as the target of 5'-tritylated deoxyuridine analogues with anti-malarial activity.Malaria journal · 2019Article
- Tocopherol biosynthesis inFEBS open bio · 2019Article
- De novo biosynthesis of sterols and fatty acids in the Trypanosoma brucei procyclic form: Carbon source preferences and metabolic flux redistributions.PLoS pathogens · 2018Article
- Molecular Characterization ofFrontiers in cellular and infection microbiology · 2018Article
- Induction of mitochondrial dysfunction and oxidative stress in Leishmania donovani by orally active clerodane diterpene.Antimicrobial agents and chemotherapy · 2014Article
- Trypanosoma cruzi response to sterol biosynthesis inhibitors: morphophysiological alterations leading to cell death.PloS one · 2013Article
- Targeting Trypanosoma cruzi sterol 14α-demethylase (CYP51).Advances in parasitology · 2011Review
- Sterol 14alpha-demethylase (CYP51) as a therapeutic target for human trypanosomiasis and leishmaniasis.Current topics in medicinal chemistry · 2011Review
- Structural insights into inhibition of sterol 14alpha-demethylase in the human pathogen Trypanosoma cruzi.The Journal of biological chemistry · 2010Article
- Lipid metabolism in Trypanosoma brucei.Molecular and biochemical parasitology · 2010Review
- Rewiring and regulation of cross-compartmentalized metabolism in protists.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2010Review
- Sterol Biosynthesis Pathway as Target for Anti-trypanosomatid Drugs.Interdisciplinary perspectives on infectious diseases · 2009Article
- Farnesyl diphosphate synthase localizes to the cytoplasm of Trypanosoma cruzi and T. brucei.Experimental parasitology · 2008Article
- Sterol 14alpha-demethylase cytochrome P450 (CYP51), a P450 in all biological kingdoms.Biochimica et biophysica acta · 2007Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
3-Hydroxy-3-methyl-glutaryl-CoA reductase (HMGR) is a key enzyme in the sterol biosynthesis pathway, but its subcellular distribution in the Trypanosomatidae family is somewhat controversial. Trypanosoma cruzi and Leishmania HMGRs are closely related in their catalytic domains to bacterial and eukaryotic enzymes described but lack an amino-terminal domain responsible for the attachment to the endoplasmic reticulum. In the present study, digitonin-titration experiments together with immunoelectron microscopy were used to establish the intracellular localization of HMGR in these pathogens. Results obtained with wild-type cells and transfectants overexpressing the enzyme established that HMGR in both T. cruzi and Leishmania major is localized primarily in the mitochondrion and that elimination of the mitochondrial targeting sequence in Leishmania leads to protein accumulation in the cytosolic compartment. Furthermore, T. cruzi HMGR is efficiently targeted to the mitochondrion in yeast cells. Thus, when the gene encoding T. cruzi HMGR was expressed in a hmg1 hmg2 mutant of Saccharomyces cerevisiae, the mevalonate auxotrophy of mutant cells was relieved, and immunoelectron analysis showed that the parasite enzyme exhibits a mitochondrial localization, suggesting a conservation between the targeting signals of both organisms.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.