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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...

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Autores principales: Gellerich, Frank Norbert, Gizatullina, Zemfira, Arandarcikaite, Odeta, Jerzembek, Doreen, Vielhaber, Stefan, Seppet, Enn, Striggow, Frank
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2009
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+).
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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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