| Autor: |
Markus Waldeck-Weiermair, Benjamin Gottschalk, Corina T. Madreiter-Sokolowski, Jeta Ramadani-Muja, Gabriela Ziomek, Christiane Klec, Sandra Burgstaller, Helmut Bischof, Maria R. Depaoli, Emrah Eroglu, Roland Malli, Wolfgang F. Graier |
| Jazyk: |
angličtina |
| Rok vydání: |
2019 |
| Předmět: |
|
| Zdroj: |
Frontiers in Cellular Neuroscience, Vol 13 (2019) |
| Druh dokumentu: |
article |
| ISSN: |
1662-5102 |
| DOI: |
10.3389/fncel.2019.00449 |
| Popis: |
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. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
|
