Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Bachkoenig, O.
The translation of IP3-triggered Ca2+ release from the ER to the Mitochondria points out the tight connection of the two organelles
PhD-Studium (Doctor of Philosophy); Humanmedizin; [ Dissertation ] Medizinische Universität Graz; 2025. pp.
- Autor*innen der Med Uni Graz:
- Betreuer*innen:
- Graier Wolfgang
- Groschner Klaus
- Madreiter-Sokolowski Corina
- Altmetrics:
- Abstract:
- Mitochondria play an essential role in cellular Ca2+ signaling. They serve as Ca2+ buffers, initiate apoptotic cell death, and are a central hub for cellular metabolism. The uptake of Ca2+ into the mitochondrial matrix is highly regulated by the mitochondrial calcium uniporter complex (MCUC), a multiprotein complex in the inner mitochondrial membrane. The MCUC consists of the pore-forming protein MCU, the dominant negative subunit MCUb, its essential regulator EMRE, the so-called gatekeepers MICU1 and 2, the assembly factor MCUR1, and, under certain conditions like cancer or aging, the uncoupling proteins UCP2/3. Opening of the MCUC is facilitated by local Ca2+ hotspots, which lead to Ca2+ binding to the EF-hand domains of the MICUs and a subsequent conformational change. In this work, I studied the translation of cytosolic Ca2+ signals from different sources, including the endoplasmatic reticulum (ER) and extracellular space via the store-operated Ca2+ entry (SOCE), to the mitochondrial matrix. I used different concentrations of the IP3-generating agent histamine and the antipsychotic drug risperidone, which exhibits antihistaminic side effects, and correlated the changes in cytosolic Ca2+ signals with those in the mitochondrial matrix. My results confirm the necessity of a cytosolic Ca2+ threshold for achieving activation of mitochondrial Ca2+ uptake and support the hypothesis of source-dependent mitochondrial Ca2+ uptake.