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Waldeck-Weiermair, M; Gottschalk, B; Madreiter-Sokolowski, CT; Ramadani-Muja, J; Ziomek, G; Klec, C; Burgstaller, S; Bischof, H; Depaoli, MR; Eroglu, E; Malli, R; Graier, WF.
Development and Application of Sub-Mitochondrial Targeted Ca2 + Biosensors.
Front Cell Neurosci. 2019; 13: 449-449.
Doi: 10.3389/fncel.2019.00449
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- Führende Autor*innen der Med Uni Graz
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Waldeck-Weiermair Markus
- Co-Autor*innen der Med Uni Graz
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Bischof Helmut
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Burgstaller Sandra
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Depaoli Maria Rosa
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EROGLU Emrah
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Gottschalk Benjamin
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Graier Wolfgang
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Klec Christiane
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Madreiter-Sokolowski Corina
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Malli Roland
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Ramadani-Muja Jeta
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Ziomek Gabriela
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- Abstract:
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Mitochondrial Ca2+ uptake into the mitochondrial matrix is a well-established mechanism. However, the sub-organellar Ca2+ kinetics remain elusive. In the present work we identified novel site-specific targeting sequences for the intermembrane space (IMS) and the cristae lumen (CL). We used these novel targeting peptides to develop green- and red- Ca2+ biosensors targeted to the IMS and to the CL. Based on their distinctive spectral properties, and comparable sensitivities these novel constructs were suitable to visualize Ca2+-levels in various (sub) compartments in a multi-chromatic manner. Functional studies that applied these new biosensors revealed that knockdown of MCU and EMRE yielded elevated Ca2+ levels inside the CL but not the IMS in response to IP3-generating agonists. Knockdown of VDAC1, however, strongly impeded the transfer of Ca2+ through the OMM while the cytosolic Ca2+ signal remained unchanged. The novel sub-mitochondrially targeted Ca2+ biosensors proved to be suitable for Ca2+ imaging with high spatial and temporal resolution in a multi-chromatic manner allowing simultaneous measurements. These informative biosensors will facilitate efforts to dissect the complex sub-mitochondrial Ca2+ signaling under (patho)physiological conditions.
Copyright © 2019 Waldeck-Weiermair, Gottschalk, Madreiter-Sokolowski, Ramadani-Muja, Ziomek, Klec, Burgstaller, Bischof, Depaoli, Eroglu, Malli and Graier.
- Find related publications in this database (Keywords)
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Ca2+ measurements
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biosensors
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mitochondrial Ca2+
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mitochondrial cristae
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Ca2+
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live cell imaging
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mitochondria