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Mitochondrial Localization of the Mevalonate Pathway Enzyme 3-Hydroxy-3-methyl-glutaryl-CoA Reductase in the Trypanosomatidae

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dc.creator Peña Díaz, Javier
dc.creator Montalvetti, Andrea
dc.creator Flores, Carmen-Lisset
dc.creator Constán Gutiérrez, Aurora Isabel
dc.creator Hurtado Guerrero, Ramón
dc.creator Souza, Wanderley de
dc.creator Gancedo, Carlos
dc.creator Ruiz Pérez, Luis M.
dc.creator González-Pacanowska, D.
dc.date 2008-06-26T07:43:50Z
dc.date 2008-06-26T07:43:50Z
dc.date 2004-03
dc.date.accessioned 2017-01-31T01:54:15Z
dc.date.available 2017-01-31T01:54:15Z
dc.identifier Mol Biol Cell. 2004 March; 15(3): 1356–1363
dc.identifier 1059-1524
dc.identifier http://hdl.handle.net/10261/5354
dc.identifier 10.1091/mbc.E03-10-0720
dc.identifier.uri http://dspace.mediu.edu.my:8181/xmlui/handle/10261/5354
dc.description Copyright © by American Society for Cell Biology.-- Final full-text version of the paper available at: http://www.molbiolcell.org/content/vol15/issue3/
dc.description 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.
dc.description This work was supported by grants from the UNDP/World Bank/World Health Organization Program for Research and Training in Tropical diseases (T24/181/30 ID 980139), the Spanish Programa Nacional de Biotecnología (BIO97-0659), the EC INCO-DC project contract no. CT980371, and the Plan Andaluz de Investigación (Cod. CVI-199). J.P. and R.H. are fellows of the Spanish PFPI of the Ministerio de Educación y Ciencia, A.M. and C.F.L. had a fellowship from the Instituto deCooperacion Iberoamericana (Spain).
dc.description Peer reviewed
dc.format 299032 bytes
dc.format application/pdf
dc.language eng
dc.publisher American Society for Cell Biology
dc.rights openAccess
dc.title Mitochondrial Localization of the Mevalonate Pathway Enzyme 3-Hydroxy-3-methyl-glutaryl-CoA Reductase in the Trypanosomatidae
dc.type Artículo

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