T3-induced rewiring of mitochondrial Ca2+ in cancer cells

Balanced mitochondrial calcium homeostasis is essential to cancer cells. Calcium facilitates the metabolic activity of the mitochondria and, thus, the cellular energy supply. However, mitochondrial calcium overload leads to cell death. Therefore, in cancer cells, calcium uptake is tightly controlled via the mitochondrial calcium uniporter (MCU), and the interaction between mitochondria and the largest intracellular calcium store, the endoplasmic reticulum (ER), is dynamically adjusted. We recently demonstrated that the thyroid hormone triiodothyronine (T3) increases mitochondrial calcium uptake and thereby drives mitochondrial energy supply and the formation of reactive oxygen species. The current project investigates how T3 modulates mitochondrial calcium homeostasis in different cancer cells and whether altered calcium uptake affects metabolic activity and cancer cell survival, proliferation, and migration. To identify targets for new therapeutic strategies, the underlying signal cascades, which are triggered by short-term and long-term T3 application, will also be analyzed. Cutting-edge methods of fluorescence microscopy and the patch-clamp technique will be applied to investigate the interplay between thyroid hormones and cellular calcium homeostasis in living cells. Standard methods of molecular and cell biology, such as western blots or proliferation and migration assays, will supplement these experiments. The project is led by Corina Madreiter-Sokolowski, Associate Professor at the Medical University of Graz, and aims to identify targets for novel strategies in cancer treatment.