Selected Publication:
Tawfik, I.
T3-induced upregulation of UCP2 as a boost for mitochondrial metabolism via enhanced mitochondrial Ca2+ uptake.
[ Diplomarbeit/Master Thesis (UNI) ] TU Graz; 2021.
FullText
- Authors Med Uni Graz:
- Advisor:
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Madreiter-Sokolowski Corina
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- Abstract:
- Triiodothyronine (T3) induces upregulation of uncoupling proteins 2 and 3 (UCP2/3) in various cell types. Despite a predicted uncoupling function of UCP2 and UCP3, upregulation of these proteins is associated with increased mitochondrial adeno-sine triphosphate (ATP) production. Notably, several groups failed to deliver evi-dence for the uncoupling function of UCP2 and UCP3, proposed due to their se-quence similarity to the well-known uncoupling protein 1 (UCP1). In 2007, live-cell imaging experiments revealed that UCP2 and UCP3 trigger mitochondrial calcium ([Ca2+]mito) uptake. The mitochondrial Ca2+ uptake 1 (MICU1) functions as a gate-keeper for the pore-forming mitochondrial Ca2+ uniporter (MCU) and gets desensi-tized to Ca2+ by protein methyltransferase 1 (PRMT1)-driven methylation. UCP2 and UCP3 can normalize [Ca2+]mito uptake in case of a decreased Ca2+ sensitivity due to MICU1
methylation. Notably, we found upregulation of PRMT1 and UCP2 in various can-cer types. Furthermore, we could show that PRMT1 and UCP2 ensure proper [Ca2+]mito uptake to boost the activity of Ca2+-sensitive dehydrogenases of the tri-carboxylic (TCA) cycle and, thereby, mitochondrial ATP production. (...)