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Extramitochondrial Ca(2+) in the Nanomolar Range Regulates Glutamate-Dependent Oxidative Phosphorylation on Demand
We present unexpected and novel results revealing that glutamate-dependent oxidative phosphorylation (OXPHOS) of brain mitochondria is exclusively and efficiently activated by extramitochondrial Ca(2+) in physiological concentration ranges (S(0.5) = 360 nM Ca(2+)). This regulation was not affected b...
Autores principales: | , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2009
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2784944/ https://www.ncbi.nlm.nih.gov/pubmed/20011041 http://dx.doi.org/10.1371/journal.pone.0008181 |
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author | Gellerich, Frank Norbert Gizatullina, Zemfira Arandarcikaite, Odeta Jerzembek, Doreen Vielhaber, Stefan Seppet, Enn Striggow, Frank |
author_facet | Gellerich, Frank Norbert Gizatullina, Zemfira Arandarcikaite, Odeta Jerzembek, Doreen Vielhaber, Stefan Seppet, Enn Striggow, Frank |
author_sort | Gellerich, Frank Norbert |
collection | PubMed |
description | We present unexpected and novel results revealing that glutamate-dependent oxidative phosphorylation (OXPHOS) of brain mitochondria is exclusively and efficiently activated by extramitochondrial Ca(2+) in physiological concentration ranges (S(0.5) = 360 nM Ca(2+)). This regulation was not affected by RR, an inhibitor of the mitochondrial Ca(2+) uniporter. Active respiration is regulated by glutamate supply to mitochondria via aralar, a mitochondrial glutamate/aspartate carrier with regulatory Ca(2+)-binding sites in the mitochondrial intermembrane space providing full access to cytosolic Ca(2+). At micromolar concentrations, Ca(2+) can also enter the intramitochondrial matrix and activate specific dehydrogenases. However, the latter mechanism is less efficient than extramitochondrial Ca(2+) regulation of respiration/OXPHOS via aralar. These results imply a new mode of glutamate-dependent OXPHOS regulation as a demand-driven regulation of mitochondrial function. This regulation involves the mitochondrial glutamate/aspartate carrier aralar which controls mitochondrial substrate supply according to the level of extramitochondrial Ca(2+). |
format | Text |
id | pubmed-2784944 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2009 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-27849442009-12-10 Extramitochondrial Ca(2+) in the Nanomolar Range Regulates Glutamate-Dependent Oxidative Phosphorylation on Demand Gellerich, Frank Norbert Gizatullina, Zemfira Arandarcikaite, Odeta Jerzembek, Doreen Vielhaber, Stefan Seppet, Enn Striggow, Frank PLoS One Research Article We present unexpected and novel results revealing that glutamate-dependent oxidative phosphorylation (OXPHOS) of brain mitochondria is exclusively and efficiently activated by extramitochondrial Ca(2+) in physiological concentration ranges (S(0.5) = 360 nM Ca(2+)). This regulation was not affected by RR, an inhibitor of the mitochondrial Ca(2+) uniporter. Active respiration is regulated by glutamate supply to mitochondria via aralar, a mitochondrial glutamate/aspartate carrier with regulatory Ca(2+)-binding sites in the mitochondrial intermembrane space providing full access to cytosolic Ca(2+). At micromolar concentrations, Ca(2+) can also enter the intramitochondrial matrix and activate specific dehydrogenases. However, the latter mechanism is less efficient than extramitochondrial Ca(2+) regulation of respiration/OXPHOS via aralar. These results imply a new mode of glutamate-dependent OXPHOS regulation as a demand-driven regulation of mitochondrial function. This regulation involves the mitochondrial glutamate/aspartate carrier aralar which controls mitochondrial substrate supply according to the level of extramitochondrial Ca(2+). Public Library of Science 2009-12-09 /pmc/articles/PMC2784944/ /pubmed/20011041 http://dx.doi.org/10.1371/journal.pone.0008181 Text en Gellerich et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Gellerich, Frank Norbert Gizatullina, Zemfira Arandarcikaite, Odeta Jerzembek, Doreen Vielhaber, Stefan Seppet, Enn Striggow, Frank Extramitochondrial Ca(2+) in the Nanomolar Range Regulates Glutamate-Dependent Oxidative Phosphorylation on Demand |
title | Extramitochondrial Ca(2+) in the Nanomolar Range Regulates Glutamate-Dependent Oxidative Phosphorylation on Demand |
title_full | Extramitochondrial Ca(2+) in the Nanomolar Range Regulates Glutamate-Dependent Oxidative Phosphorylation on Demand |
title_fullStr | Extramitochondrial Ca(2+) in the Nanomolar Range Regulates Glutamate-Dependent Oxidative Phosphorylation on Demand |
title_full_unstemmed | Extramitochondrial Ca(2+) in the Nanomolar Range Regulates Glutamate-Dependent Oxidative Phosphorylation on Demand |
title_short | Extramitochondrial Ca(2+) in the Nanomolar Range Regulates Glutamate-Dependent Oxidative Phosphorylation on Demand |
title_sort | extramitochondrial ca(2+) in the nanomolar range regulates glutamate-dependent oxidative phosphorylation on demand |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2784944/ https://www.ncbi.nlm.nih.gov/pubmed/20011041 http://dx.doi.org/10.1371/journal.pone.0008181 |
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