Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Waldeck-Weiermair, M; Malli, R; Parichatikanond, W; Gottschalk, B; Madreiter-Sokolowski, CT; Klec, C; Rost, R; Graier, WF.
Rearrangement of MICU1 multimers for activation of MCU is solely controlled by cytosolic Ca(2.).
Sci Rep. 2015; 5(50):15602-15602
Doi: 10.1038/srep15602
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- Führende Autor*innen der Med Uni Graz
- Graier Wolfgang
- Malli Roland
- Waldeck-Weiermair Markus
- Co-Autor*innen der Med Uni Graz
- Gottschalk Benjamin
- Klec Christiane
- Madreiter-Sokolowski Corina
- Parichatikanond Warisara
- Rost René
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- Abstract:
- Mitochondrial Ca(2+) uptake is a vital process that controls distinct cell and organelle functions. Mitochondrial calcium uptake 1 (MICU1) was identified as key regulator of the mitochondrial Ca(2+) uniporter (MCU) that together with the essential MCU regulator (EMRE) forms the mitochondrial Ca(2+) channel. However, mechanisms by which MICU1 controls MCU/EMRE activity to tune mitochondrial Ca(2+) signals remain ambiguous. Here we established a live-cell FRET approach and demonstrate that elevations of cytosolic Ca(2+) rearranges MICU1 multimers with an EC50 of 4.4 μM, resulting in activation of mitochondrial Ca(2+) uptake. MICU1 rearrangement essentially requires the EF-hand motifs and strictly correlates with the shape of cytosolic Ca(2+) rises. We further show that rearrangements of MICU1 multimers were independent of matrix Ca(2+) concentration, mitochondrial membrane potential, and expression levels of MCU and EMRE. Our experiments provide novel details about how MCU/EMRE is regulated by MICU1 and an original approach to investigate MCU/EMRE activation in intact cells.
- Find related publications in this database (using NLM MeSH Indexing)
- Calcium - metabolism
- Calcium Channels - biosynthesis
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- Calcium-Binding Proteins - genetics
- Calcium-Binding Proteins - metabolism
- Cation Transport Proteins - genetics
- Cation Transport Proteins - metabolism
- Cytosol - metabolism
- HEK293 Cells -
- HeLa Cells -
- Humans -
- Membrane Potential, Mitochondrial - genetics
- Mitochondria - genetics
- Mitochondria - metabolism
- Mitochondrial Membrane Transport Proteins - genetics
- Mitochondrial Membrane Transport Proteins - metabolism
- Protein Multimerization - genetics