Nuclear receptors and other nuclear transcription factors in mitochondria: Regulatory molecules in a new environment

AbstractThe mitochondrion is the major energy generating organelle of the cell and the site of other basic processes, including apoptosis. The mitochondrial functions are performed in concert with other cell compartments and are regulated by various extracellular and intracellular signals. Several nuclear receptors and other nuclear transcription factors, such as NF-κB, AP-1, CREB and p53, involved in growth, metabolic and developmental processes, have been detected in mitochondria. This finding raises the question as to the role of these regulatory molecules in their “new” environment. Experimental evidence supports the action of the mitochondrially localized transcription factors on mitochondrial transcription, energy yield and apoptosis, extending the known nuclear role of these molecules outside the nucleus. A principle of coordination of nuclear and mitochondrial gene transcription has been ascertained as regards the regulatory action of steroid and thyroid hormones on energy yield. Accordingly, the same nuclear receptors, localized in the two compartments–nuclei and mitochondria–regulate transcription of genes serving a common function by way of interaction with common binding sites in the two genomes. This principle is now expanding to encompass other nuclearly and mitochondrially localized transcription factors

Glucocorticoid and Estrogen Receptors Are Reduced in Mitochondria of Lung Epithelial Cells in Asthma

Mitochondrial glucocorticoid (mtGR) and estrogen (mtER) receptors participate in the coordination of the cell’s energy requirement and in the mitochondrial oxidative phosphorylation enzyme (OXPHOS) biosynthesis, affecting reactive oxygen species (ROS) generation and induction of apoptosis. Although activation of mtGR and mtER is known to trigger anti-inflammatory signals, little information exists on the presence of these receptors in lung tissue and their role in respiratory physiology and disease. Using a mouse model of allergic airway inflammation disease and applying confocal microscopy, subcellular fractionation, and Western blot analysis we showed mitochondrial localization of GRα and ERβ in lung tissue. Allergic airway inflammation caused reduction in mtGRα, mtERβ, and OXPHOS enzyme biosynthesis in lung cells mitochondria and particularly in bronchial epithelial cells mitochondria, which was accompanied by decrease in lung mitochondrial mass and induction of apoptosis. Confirmation and validation of the reduction of the mitochondrial receptors in lung epithelial cells in human asthma was achieved by analyzing autopsies from fatal asthma cases. The presence of the mitochondrial GRα and ERβ in lung tissue cells and especially their reduction in bronchial epithelial cells during allergic airway inflammation suggests a crucial role of these receptors in the regulation of mitochondrial function in asthma, implicating their involvement in the pathophysiology of the disease

The Distribution and Properties of the Glucocorticoid Receptor from Rat-Brain and Pituitary

Journal URL: http://www.jbc.org

Hnrna - Snrna - Protein Complexes - Possible Structure and Function

Journal URL: http://mcc.irb.hr/instruct.htm

Glucocorticoid Receptor Structure as Probed by Endogenous Proteases

Journal URL: http://www.sciencedirect.com/science/journal/0022473

Association of Small Nuclear-Rna with Hnrna Isolated from Nuclear Rnp Complexes Carrying Hnrna

Journal URL: http://www.sciencedirect.com/science/journal/0014579

Detection of oestrogen receptor variants in endometrium, myometrium, leiomyoma and peripheral blood mononuclear cells: comparison to variants present in breast cancer

Journal URL: http://www.springerlink.com/content/101168

Tumour-associated trypsin inhibitor, carcinoembryonic antigen and acute-phase reactant proteins CRP and alpha 1-antitrypsin in patients with gastrointestinal malignancies

Journal URL: http://www.sciencedirect.com/science/journal/0009912

The Detection of Glucocorticoid Receptors in Breast-Cancer by Immuno-Cytochemical and Biochemical Methods

Journal URL: http://www3.interscience.wiley.com/journal/29331/hom