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Selected Publication:
SHR Neuro Cancer Cardio Lipid Metab Microb
Deak, AT; Blass, S; Khan, MJ; Groschner, LN; Waldeck-Weiermair, M; Hallström, S; Graier, WF; Malli, R.
IP3-mediated STIM1 oligomerization requires intact mitochondrial Ca2+ uptake.
J Cell Sci. 2014; 127(Pt 13):2944-2955
Doi: 10.1242/jcs.149807
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- Leading authors Med Uni Graz
- Deak Andras Tamas
- Malli Roland
- Co-authors Med Uni Graz
- Blass Sandra
- Graier Wolfgang
- Groschner Lukas
- Hallström Seth
- Khan Muhammad Jadoon
- Waldeck-Weiermair Markus
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- Abstract:
- Mitochondria contribute to cell signaling by controlling store-operated Ca(2+) entry (SOCE). SOCE is activated by Ca(2+) release from the endoplasmic reticulum (ER), whereupon stromal interacting molecule 1 (STIM1) forms oligomers, redistributes to ER-plasma-membrane junctions and opens plasma membrane Ca(2+) channels. The mechanisms by which mitochondria interfere with the complex process of SOCE are insufficiently clarified. In this study, we used an shRNA approach to investigate the direct involvement of mitochondrial Ca(2+) buffering in SOCE. We demonstrate that knockdown of either of two proteins that are essential for mitochondrial Ca(2+) uptake, the mitochondrial calcium uniporter (MCU) or uncoupling protein 2 (UCP2), results in decelerated STIM1 oligomerization and impaired SOCE following cell stimulation with an inositol-1,4,5-trisphosphate (IP3)-generating agonist. Upon artificially augmented cytosolic Ca(2+) buffering or ER Ca(2+) depletion by sarcoplasmic or endoplasmic reticulum Ca(2+)-ATPase (SERCA) inhibitors, STIM1 oligomerization did not rely on intact mitochondrial Ca(2+) uptake. However, MCU-dependent mitochondrial sequestration of Ca(2+) entering through the SOCE pathway was essential to prevent slow deactivation of SOCE. Our findings show a stimulus-specific contribution of mitochondrial Ca(2+) uptake to the SOCE machinery, likely through a role in shaping cytosolic Ca(2+) micro-domains. © 2014. Published by The Company of Biologists Ltd.
- Find related publications in this database (using NLM MeSH Indexing)
- Calcium - metabolism
- Calcium Channels - genetics
- Calcium Channels - metabolism
- Calcium Signaling -
- HeLa Cells -
- Humans -
- Inositol 1,4,5-Trisphosphate - genetics
- Inositol 1,4,5-Trisphosphate - metabolism
- Membrane Proteins - genetics
- Membrane Proteins - metabolism
- Mitochondria - metabolism
- Neoplasm Proteins - genetics
- Neoplasm Proteins - metabolism
- Stromal Interaction Molecule 1 -
- Find related publications in this database (Keywords)
- Mitochondrial Ca2+ uptake
- UCP2
- MCU
- SOCE
- STIM1 oligomerization