Overexpression of STIM1 and its impact on mitochondrial metabolism

Calcium (Ca²⁺) is ubiquitously the second messenger involved in the regulation of many cell functions such as proliferation, differentiation, apoptosis, exocytosis, muscle contraction, and so on. The main organelle linked to calcium metabolism is the mitochondria. The influx of Ca²⁺ into the cells is mediated by store-operated calcium entry (SOCE), which is activated by the lack of intracellular storage of Ca²⁺. The sensor protein-stromal interaction molecule 1 (STIM1) and the ion channel ORAI1 are key players in the physiological function of SOCE. Mutation of the luminal EF-hand motif of STIM1 generates a constitutively active STIM1 and activates Ca²⁺ entry independently from the endoplasmic reticulum (ER) stores of Ca²⁺. In our project, we create the functional STIM1 cell model that will be used for the detection of changes related to continuous SOCE activation caused by STIM1 overexpression in the Tet-on inducible expression system in human embryonic kidney cells (HEK293). We assume, that this model creates a suitable environment for monitoring the impact as well as communication between cellular Ca²⁺ entry mediated by STIM1 and intracellular organelles such as mitochondria. Moreover, communication between these organelles has a direct impact on mitochondrial metabolism, shape, bioenergetics, or stress response, all involved in the development of disease-related pathological changes.