T3-induced enhancement of mitochondrial Ca2+ uptake as a boost for mitochondrial metabolism.

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.

• Publication year

  2022

• Venue

  Free Radical Biology & Medicine

• Publication date

  2022-01-01

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1016/j.freeradbiomed.2022.01.024PMID 35091061
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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