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rdf:type |
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lifeskim:mentions |
umls-concept:C0001480,
umls-concept:C0017262,
umls-concept:C0033268,
umls-concept:C0085080,
umls-concept:C0085845,
umls-concept:C0185117,
umls-concept:C0220839,
umls-concept:C0332324,
umls-concept:C0442805,
umls-concept:C0521451,
umls-concept:C0560175,
umls-concept:C1706209,
umls-concept:C2911684
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pubmed:issue |
40
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pubmed:dateCreated |
2003-9-29
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pubmed:databankReference |
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pubmed:abstractText |
The Ca(2+)-sensitive dehydrogenases of the mitochondrial matrix are, so far, the only known effectors to allow Ca2+ signals to couple the activation of plasma membrane receptors to the stimulation of aerobic metabolism. In this study, we demonstrate a novel mechanism, based on Ca(2+)-sensitive metabolite carriers of the inner membrane. We expressed in Chinese hamster ovary cells aralar1 and citrin, aspartate/glutamate exchangers that have Ca(2+)-binding sites in their sequence, and measured mitochondrial Ca2+ and ATP levels as well as cytosolic Ca2+ concentration with targeted recombinant probes. The increase in mitochondrial ATP levels caused by cell stimulation with Ca(2+)-mobilizing agonists was markedly larger in cells expressing aralar and citrin (but not truncated mutants lacking the Ca(2+)-binding site) than in control cells. Conversely, the cytosolic and the mitochondrial Ca2+ signals were the same in control cells and cells expressing the different aralar1 and citrin variants, thus ruling out an indirect effect through the Ca(2+)-sensitive dehydrogenases. Together, these data show that the decoding of Ca2+ signals in mitochondria depends on the coordinate activity of mitochondrial enzymes and carriers, which may thus represent useful pharmacological targets in this process of major pathophysiological interest.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Adenosine Triphosphate,
http://linkedlifedata.com/resource/pubmed/chemical/Aequorin,
http://linkedlifedata.com/resource/pubmed/chemical/Aspartic Acid,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Glutamic Acid,
http://linkedlifedata.com/resource/pubmed/chemical/Luciferases,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Transport Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Mitochondrial Membrane Transport...,
http://linkedlifedata.com/resource/pubmed/chemical/Mitochondrial Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Organic Anion Transporters,
http://linkedlifedata.com/resource/pubmed/chemical/Oxygen,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/SLC25A12 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/citrin
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pubmed:status |
MEDLINE
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pubmed:month |
Oct
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pubmed:issn |
0021-9258
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
3
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pubmed:volume |
278
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
38686-92
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:12851387-Adenosine Triphosphate,
pubmed-meshheading:12851387-Aequorin,
pubmed-meshheading:12851387-Animals,
pubmed-meshheading:12851387-Aspartic Acid,
pubmed-meshheading:12851387-Binding Sites,
pubmed-meshheading:12851387-Blotting, Western,
pubmed-meshheading:12851387-CHO Cells,
pubmed-meshheading:12851387-Calcium,
pubmed-meshheading:12851387-Calcium-Binding Proteins,
pubmed-meshheading:12851387-Cell Membrane,
pubmed-meshheading:12851387-Cricetinae,
pubmed-meshheading:12851387-Cytosol,
pubmed-meshheading:12851387-Glutamic Acid,
pubmed-meshheading:12851387-Humans,
pubmed-meshheading:12851387-Luciferases,
pubmed-meshheading:12851387-Luminescent Measurements,
pubmed-meshheading:12851387-Membrane Transport Proteins,
pubmed-meshheading:12851387-Microscopy, Fluorescence,
pubmed-meshheading:12851387-Mitochondria,
pubmed-meshheading:12851387-Mitochondrial Membrane Transport Proteins,
pubmed-meshheading:12851387-Mitochondrial Proteins,
pubmed-meshheading:12851387-Molecular Sequence Data,
pubmed-meshheading:12851387-Organic Anion Transporters,
pubmed-meshheading:12851387-Oxygen,
pubmed-meshheading:12851387-Plasmids,
pubmed-meshheading:12851387-Protein Structure, Tertiary,
pubmed-meshheading:12851387-Recombinant Proteins,
pubmed-meshheading:12851387-Spectrometry, Fluorescence,
pubmed-meshheading:12851387-Transfection
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pubmed:year |
2003
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pubmed:articleTitle |
Recombinant expression of the Ca(2+)-sensitive aspartate/glutamate carrier increases mitochondrial ATP production in agonist-stimulated Chinese hamster ovary cells.
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pubmed:affiliation |
Department of Pharmaco-Biology, Laboratory of Biochemistry and Molecular Biology, University of Bari and CNR Institute of Biomembranes and Bioenergetics, Via Orabona 4, 70125 Bari, Italy.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, Non-P.H.S.,
Research Support, Non-U.S. Gov't
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