Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Waldeck-Weiermair, M; Deak, AT; Groschner, LN; Alam, MR; Jean-Quartier, C; Malli, R; Graier, WF.
Molecularly distinct routes of mitochondrial Ca2+ uptake are activated depending on the activity of the sarco/endoplasmic reticulum Ca2+ ATPase (SERCA).
J Biol Chem. 2013; 288(21):15367-15379
Doi: 10.1074/jbc.M113.462259
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- Führende Autor*innen der Med Uni Graz
- Deak Andras Tamas
- Graier Wolfgang
- Waldeck-Weiermair Markus
- Co-Autor*innen der Med Uni Graz
- Alam Muhammad Rizwan
- Groschner Lukas
- Jean-Quartier Claire
- Malli Roland
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- Abstract:
- 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.
- Find related publications in this database (using NLM MeSH Indexing)
- Calcium - metabolism
- Calcium Signaling - physiology
- Endoplasmic Reticulum - genetics Endoplasmic Reticulum - metabolism
- HeLa Cells -
- Humans -
- Ion Channels - genetics Ion Channels - metabolism
- Mitochondria - genetics Mitochondria - metabolism
- Mitochondrial Membranes - metabolism
- Mitochondrial Proteins - genetics Mitochondrial Proteins - metabolism
- Sarcoplasmic Reticulum Calcium-Transporting ATPases - genetics Sarcoplasmic Reticulum Calcium-Transporting ATPases - metabolism