Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Bachkoenig, OA; Gottschalk, B; Malli, R; Graier, WF.
An unexpected effect of risperidone reveals a nonlinear relationship between cytosolic Ca2+ and mitochondrial Ca2+ uptake.
Curr Top Membr. 2022; 90: 13-35.
Doi: 10.1016/bs.ctm.2022.09.001
PubMed
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- Führende Autor*innen der Med Uni Graz
- Bachkönig Olaf Arne Georg
- Graier Wolfgang
- Co-Autor*innen der Med Uni Graz
- Gottschalk Benjamin
- Malli Roland
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- Abstract:
- Mitochondria actively contribute to cellular Ca2+ homeostasis. The molecular mechanisms of mitochondrial Ca2+ uptake and release are well characterized and are attributed to the multi-protein assembly of the mitochondrial Ca2+ uniporter complex (MCUC) and the mitochondrial sodium-calcium exchanger (NCLX), respectively. Hence, Ca2+ transfer from the endoplasmic reticulum (ER) and store-operated Ca2+ entry (SOCE) into the mitochondrial matrix has been quantitatively visualized on the subcellular level using targeted fluorescent biosensors. However, a correlation between the amplitude of cytosolic Ca2+ elevation with that in the mitochondrial matrix has not been investigated in detail so far. In the present study, we combined the Ca2+-mobilizing agonist histamine with the H1-receptor antagonist risperidone to establish a well-tunable experimental approach allowing the correlation between low, slow, high, and fast cytosolic and mitochondrial Ca2+ signals in response to inositol 1,4,5-trisphosphate (IP3)-triggered ER Ca2+ release. Our present data confirm a defined threshold in cytosolic Ca2+, which is necessary for the activation of mitochondrial Ca2+ uptake. Moreover, our data support the hypothesis of different modes of mitochondrial Ca2+ uptake depending on the source of the ion (i.e., ER vs SOCE).
- Find related publications in this database (using NLM MeSH Indexing)
- Calcium Signaling - administration & dosage
- Risperidone - pharmacology, metabolism
- Calcium - metabolism
- Cytosol - metabolism
- Mitochondria - metabolism