Abstract
Mitochondria are membrane organelles present in almost all eukaryotic cells. In addition to their well-known role in energy production, mitochondria regulate central cellular processes, including calcium homeostasis, Reactive Oxygen Species (ROS) generation, cell death, thermogenesis, and biosynthesis of lipids, nucleic acids, and steroid hormones. Glucocorticoids (GCs) regulate the mitochondrially encoded oxidative phosphorylation gene expression and mitochondrial energy metabolism. The identification of Glucocorticoid Response Elements (GREs) in mitochondrial sequences and the detection of Glucocorticoid Receptor (GR) in mitochondria of different cell types gave support to hypothesis that mitochondrial GR directly regulates mitochondrial gene expression. Numerous studies have revealed changes in mitochondrial gene expression alongside with GR import/export in mitochondria, confirming the direct effects of GCs on mitochondrial genome. Further evidence has made clear that mitochondrial GR is involved in mitochondrial function and apoptosis-mediated processes, through interacting or altering the distribution of Bcl2 family members. Even though its exact translocation mechanisms remain unknown, data have shown that GR chaperones (Hsp70/90, Bag-1, FKBP51), the anti-apoptotic protein Bcl-2, the HDAC6- mediated deacetylation and the outer mitochondrial translocation complexes (Tom complexes) co-ordinate GR mitochondrial trafficking. A role of mitochondrial GR in stress and depression as well as in lung and hepatic inflammation has also been demonstrated.
Highlights
Mitochondria are membrane organelles present in almost all eukaryotic cells
Talabér et al revealed that Dex-treated CD4+CD8+ double-positive thymocytes were characterized by reduced mitochondrial membrane potential in parallel with Glucocorticoid Receptor (GR) translocation into the mitochondria [61].To elucidate the mitochondrial apoptotic pathway involved in GC-induced thymocyte apoptosis, Prenek et al investigated the interactions between GR and Bcl-2 family proteins in Dex-treated mouse thymocytes, including Bak, Bim, and Bcl-xL [62]
In order to elucidate the mechanisms underlying the biphasic effects of GCs on mitochondrial function and neuronal viability/apoptosis, they investigated time and dose effects of Cort on mitochondrial translocation of glucocorticoid receptors (GRs); their study revealed that both low and high doses of Cort enhanced the mitochondrial localization of GRs whereas after long-term treatment with high doses of Cort, mitochondrial localization of GRs is reduced, suggesting that GRs translocate into mitochondria in a dose- and time-dependent manner
Summary
Mitochondria are multifunctional life-sustaining organelles that contain several identical copies of their own genome—the mitochondrial DNA (mtDNA). They are present in almost every eukaryotic cell type, except red blood cells, and they exhibit several features of their bacterial origin [1]. Even though the exact role of the ORF-derived peptides remains unknown, studies have shown that these peptides participate in the regulation of mitochondrial function while their dysregulation has been associated with the development of metabolic and cardiovascular disorders [13,14]
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