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SHR Neuro Krebs Kardio Lipid

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 [OPEN ACCESS]
Web of Science PubMed PUBMED Central FullText FullText_MUG

 

Autor/innen der Med Uni Graz:
Blass Sandra
Deak Andras Tamas
Graier Wolfgang
Groschner Lukas
Hallström Seth
Khan Muhammad Jadoon
Malli Roland
Waldeck-Weiermair Markus
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Number of Figures: 7
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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.

Find related publications in this database (Keywords)
Mitochondrial Ca2+ uptake
UCP2
MCU
SOCE
STIM1 oligomerization
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