Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Tawfik, I; Gottschalk, B; Jarc, A; Bresilla, D; Rost, R; Obermayer-Pietsch, B; Graier, WF; Madreiter-Sokolowski, CT.
T3-induced enhancement of mitochondrial Ca2+ uptake as a boost for mitochondrial metabolism.
Free Radic Biol Med. 2022; 181:197-208
Doi: 10.1016/j.freeradbiomed.2022.01.024
Web of Science
PubMed
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- Führende Autor*innen der Med Uni Graz
- Gottschalk Benjamin
- Madreiter-Sokolowski Corina
- Tawfik Ines
- Co-Autor*innen der Med Uni Graz
- Graier Wolfgang
- Jarc Angelo
- Obermayer-Pietsch Barbara
- Rost René
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- Abstract:
- Thyroid hormones act as master regulators of cellular metabolism. Thereby, the biologically active triiodothyronine (T3) induces the expression of genes to enhance mitochondrial metabolic function. Notably, Ca2+ ions are necessary for the activity of dehydrogenases of the tricarboxylic acid cycle and, thus, mitochondrial respiration. We investigated whether treating HeLa cells with T3 causes alterations in mitochondrial Ca2+ ([Ca2+]mito) levels. Real-time measurements by fluorescence microscopy revealed that treatment with T3 for 3 h induces a significant increase in basal [Ca2+]mito levels and [Ca2+]mito uptake upon the depletion of the endoplasmic reticulum (ER) Ca2+ store, while cytosolic Ca2+ levels remained unchanged. T3 incubation was found to upregulate mRNA expression levels of uncoupling proteins 2 and 3 (UCP2, UCP3) and of protein arginine methyltransferase 1 (PRMT1). Live-cell imaging revealed that T3-induced enhancement of mitochondrial Ca2+ uptake depends on the mitochondrial Ca2+ uniporter (MCU), UCP2, and PRMT1 that are essential for increased mitochondrial ATP ([ATP]mito) production after T3 treatment. Besides, increased [Ca2+]mito and [ATP]mito levels correlated with enhanced production of reactive oxygen species (ROS) in mitochondria. Notably, ROS scavenging causes mitochondrial Ca2+ elevation and outplays the impact of T3 on [Ca2+]mito homeostasis. Based on these results, we assume that thyroid hormones adjust [Ca2+]mito homeostasis by modulating the UCP2- and PRMT1-balanced [Ca2+]mito uptake via MCU in case of physiological ROS levels to convey their impact on mitochondrial ATP and ROS production.
- Find related publications in this database (using NLM MeSH Indexing)
- Calcium - metabolism
- HeLa Cells - administration & dosage
- Homeostasis - administration & dosage
- Humans - administration & dosage
- Mitochondria - metabolism
- Mitochondrial Proteins - genetics, metabolism
- Protein-Arginine N-Methyltransferases - metabolism
- Reactive Oxygen Species - metabolism
- Repressor Proteins - metabolism
- Triiodothyronine - pharmacology
- Uncoupling Protein 2 - metabolism
- Find related publications in this database (Keywords)
- Mitochondrial Ca2+ homeostasis
- Triiodothyronine
- Uncoupling protein 2
- Energy metabolism
- ROS production