| A common highly conserved cadmium detoxification mechanism from bacteria to humans: heavy metal tolerance conferred by the ATP-binding cassette (ABC) transporter SpHMT1 requires glutathione but not metal-chelating phytochelatin peptides. | |
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MedLine Citation:
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PMID: 19054771 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Cadmium poses a significant threat to human health due to its toxicity. In mammals and in bakers' yeast, cadmium is detoxified by ATP-binding cassette transporters after conjugation to glutathione. In fission yeast, phytochelatins constitute the co-substrate with cadmium for the transporter SpHMT1. In plants, a detoxification mechanism similar to the one in fission yeast is supposed, but the molecular nature of the transporter is still lacking. To investigate further the relationship between SpHMT1 and its co-substrate, we overexpressed the transporter in a Schizosaccharomyces pombe strain deleted for the phytochelatin synthase gene and heterologously in Saccharomyces cerevisiae and in Escherichia coli. In all organisms, overexpression of SpHMT1 conferred a markedly enhanced tolerance to cadmium but not to Sb(III), AgNO(3), As(III), As(V), CuSO(4), or HgCl(2). Abolishment of the catalytic activity by expression of SpHMT1(K623M) mutant suppressed the cadmium tolerance phenotype independently of the presence of phytochelatins. Depletion of the glutathione pool inhibited the SpHMT1 activity but not that of AtHMA4, a P-type ATPase, indicating that GSH is necessary for the SpHMT1-mediated cadmium resistance. In E. coli, SpHMT1 was targeted to the periplasmic membrane and led to an increased amount of cadmium in the periplasm. These results demonstrate that SpHMT1 confers cadmium tolerance in the absence of phytochelatins but depending on the presence of GSH and ATP. Our results challenge the dogma of the two separate cadmium detoxification pathways and demonstrate that a common highly conserved mechanism has been selected during the evolution from bacteria to humans. |
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Authors:
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Sandra Prévéral; Landry Gayet; Cristina Moldes; Jonathan Hoffmann; Sandra Mounicou; Antoine Gruet; Florie Reynaud; Ryszard Lobinski; Jean-Marc Verbavatz; Alain Vavasseur; Cyrille Forestier |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2008-12-02 |
Journal Detail:
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Title: The Journal of biological chemistry Volume: 284 ISSN: 0021-9258 ISO Abbreviation: J. Biol. Chem. Publication Date: 2009 Feb |
Date Detail:
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Created Date: 2009-02-16 Completed Date: 2009-04-13 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 2985121R Medline TA: J Biol Chem Country: United States |
Other Details:
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Languages: eng Pagination: 4936-43 Citation Subset: IM |
Affiliation:
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Commissariat à l'Energie Atomique (CEA) Cadarache, Service de Biologie Végétale et de Microbiologie Environnementales, Laboratoire des Echanges Membranaires et Signalisation, the CNRS, UMR Biologie Végétale et de Microbiologie Environnementales. |
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| MeSH Terms | |
Descriptor/Qualifier:
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ATP-Binding Cassette Transporters Adenosine Triphosphatases / genetics, metabolism Adenosine Triphosphate / genetics, metabolism* Amino Acid Substitution Aminoacyltransferases / genetics, metabolism Animals Arabidopsis Arabidopsis Proteins / genetics, metabolism Cadmium / pharmacology* Chelating Agents Drug Resistance, Fungal / physiology* Escherichia coli / genetics, metabolism Gene Expression Gene Knockout Techniques Glutathione / genetics, metabolism* Humans Mutation, Missense Phytochelatins* Recombinant Proteins / genetics, metabolism Saccharomyces cerevisiae / genetics, metabolism Schizosaccharomyces / genetics, metabolism* |
| Chemical | |
Reg. No./Substance:
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0/ATP-Binding Cassette Transporters; 0/Arabidopsis Proteins; 0/Chelating Agents; 0/Recombinant Proteins; 0/hmt1 protein, S pombe; 56-65-5/Adenosine Triphosphate; 70-18-8/Glutathione; 7440-43-9/Cadmium; 98726-08-0/Phytochelatins; EC 2.3.2.-/Aminoacyltransferases; EC 2.3.2.15/glutathione gamma-glutamylcysteinyltransferase; EC 3.6.1.-/Adenosine Triphosphatases; EC 3.6.1.3/HMA4 protein, Arabidopsis |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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