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Molecularly Distinct Routes of Mitochondrial Ca(2+) Uptake Are Activated Depending on the Activity of the Sarco/Endoplasmic Reticulum Ca(2+) ATPase (SERCA)
The transfer of Ca(2+) across the inner mitochondrial membrane is an important physiological process linked to the regulation of metabolism, signal transduction, and cell death. While the definite molecular composition of mitochondrial Ca(2+) uptake sites remains unknown, several proteins of the inn...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society for Biochemistry and Molecular Biology
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3663555/ https://www.ncbi.nlm.nih.gov/pubmed/23592775 http://dx.doi.org/10.1074/jbc.M113.462259 |
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author | Waldeck-Weiermair, Markus Deak, András T. Groschner, Lukas N. Alam, Muhammad Rizwan Jean-Quartier, Claire Malli, Roland Graier, Wolfgang F. |
author_facet | Waldeck-Weiermair, Markus Deak, András T. Groschner, Lukas N. Alam, Muhammad Rizwan Jean-Quartier, Claire Malli, Roland Graier, Wolfgang F. |
author_sort | Waldeck-Weiermair, Markus |
collection | PubMed |
description | The transfer of Ca(2+) across the inner mitochondrial membrane is an important physiological process linked to the regulation of metabolism, signal transduction, and cell death. While the definite molecular composition of mitochondrial Ca(2+) uptake sites remains unknown, several proteins of the inner mitochondrial membrane, that are likely to accomplish mitochondrial Ca(2+) fluxes, have been described: the novel uncoupling proteins 2 and 3, the leucine zipper-EF-hand containing transmembrane protein 1 and the mitochondrial calcium uniporter. It is unclear whether these proteins contribute to one unique mitochondrial Ca(2+) uptake pathway or establish distinct routes for mitochondrial Ca(2+) sequestration. In this study, we show that a modulation of Ca(2+) release from the endoplasmic reticulum by inhibition of the sarco/endoplasmatic reticulum ATPase modifies cytosolic Ca(2+) signals and consequently switches mitochondrial Ca(2+) uptake from an uncoupling protein 3- and mitochondrial calcium uniporter-dependent, but leucine zipper-EF-hand containing transmembrane protein 1-independent to a leucine zipper-EF-hand containing transmembrane protein 1- and mitochondrial calcium uniporter-mediated, but uncoupling protein 3-independent pathway. Thus, the activity of sarco/endoplasmatic reticulum ATPase is significant for the mode of mitochondrial Ca(2+) sequestration and determines which mitochondrial proteins might actually accomplish the transfer of Ca(2+) across the inner mitochondrial membrane. Moreover, our findings herein support the existence of distinct mitochondrial Ca(2+) uptake routes that might be essential to ensure an efficient ion transfer into mitochondria despite heterogeneous cytosolic Ca(2+) rises. |
format | Online Article Text |
id | pubmed-3663555 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | American Society for Biochemistry and Molecular Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-36635552013-05-28 Molecularly Distinct Routes of Mitochondrial Ca(2+) Uptake Are Activated Depending on the Activity of the Sarco/Endoplasmic Reticulum Ca(2+) ATPase (SERCA) Waldeck-Weiermair, Markus Deak, András T. Groschner, Lukas N. Alam, Muhammad Rizwan Jean-Quartier, Claire Malli, Roland Graier, Wolfgang F. J Biol Chem Signal Transduction The transfer of Ca(2+) across the inner mitochondrial membrane is an important physiological process linked to the regulation of metabolism, signal transduction, and cell death. While the definite molecular composition of mitochondrial Ca(2+) uptake sites remains unknown, several proteins of the inner mitochondrial membrane, that are likely to accomplish mitochondrial Ca(2+) fluxes, have been described: the novel uncoupling proteins 2 and 3, the leucine zipper-EF-hand containing transmembrane protein 1 and the mitochondrial calcium uniporter. It is unclear whether these proteins contribute to one unique mitochondrial Ca(2+) uptake pathway or establish distinct routes for mitochondrial Ca(2+) sequestration. In this study, we show that a modulation of Ca(2+) release from the endoplasmic reticulum by inhibition of the sarco/endoplasmatic reticulum ATPase modifies cytosolic Ca(2+) signals and consequently switches mitochondrial Ca(2+) uptake from an uncoupling protein 3- and mitochondrial calcium uniporter-dependent, but leucine zipper-EF-hand containing transmembrane protein 1-independent to a leucine zipper-EF-hand containing transmembrane protein 1- and mitochondrial calcium uniporter-mediated, but uncoupling protein 3-independent pathway. Thus, the activity of sarco/endoplasmatic reticulum ATPase is significant for the mode of mitochondrial Ca(2+) sequestration and determines which mitochondrial proteins might actually accomplish the transfer of Ca(2+) across the inner mitochondrial membrane. Moreover, our findings herein support the existence of distinct mitochondrial Ca(2+) uptake routes that might be essential to ensure an efficient ion transfer into mitochondria despite heterogeneous cytosolic Ca(2+) rises. American Society for Biochemistry and Molecular Biology 2013-05-24 2013-04-16 /pmc/articles/PMC3663555/ /pubmed/23592775 http://dx.doi.org/10.1074/jbc.M113.462259 Text en © 2013 by The American Society for Biochemistry and Molecular Biology, Inc. Author's Choice—Final version full access. Creative Commons Attribution Unported License (http://creativecommons.org/licenses/by/3.0/) applies to Author Choice Articles |
spellingShingle | Signal Transduction Waldeck-Weiermair, Markus Deak, András T. Groschner, Lukas N. Alam, Muhammad Rizwan Jean-Quartier, Claire Malli, Roland Graier, Wolfgang F. Molecularly Distinct Routes of Mitochondrial Ca(2+) Uptake Are Activated Depending on the Activity of the Sarco/Endoplasmic Reticulum Ca(2+) ATPase (SERCA) |
title | Molecularly Distinct Routes of Mitochondrial Ca(2+) Uptake Are Activated Depending on the Activity of the Sarco/Endoplasmic Reticulum Ca(2+) ATPase (SERCA) |
title_full | Molecularly Distinct Routes of Mitochondrial Ca(2+) Uptake Are Activated Depending on the Activity of the Sarco/Endoplasmic Reticulum Ca(2+) ATPase (SERCA) |
title_fullStr | Molecularly Distinct Routes of Mitochondrial Ca(2+) Uptake Are Activated Depending on the Activity of the Sarco/Endoplasmic Reticulum Ca(2+) ATPase (SERCA) |
title_full_unstemmed | Molecularly Distinct Routes of Mitochondrial Ca(2+) Uptake Are Activated Depending on the Activity of the Sarco/Endoplasmic Reticulum Ca(2+) ATPase (SERCA) |
title_short | Molecularly Distinct Routes of Mitochondrial Ca(2+) Uptake Are Activated Depending on the Activity of the Sarco/Endoplasmic Reticulum Ca(2+) ATPase (SERCA) |
title_sort | molecularly distinct routes of mitochondrial ca(2+) uptake are activated depending on the activity of the sarco/endoplasmic reticulum ca(2+) atpase (serca) |
topic | Signal Transduction |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3663555/ https://www.ncbi.nlm.nih.gov/pubmed/23592775 http://dx.doi.org/10.1074/jbc.M113.462259 |
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