The Effects of Steroid Hormones on the Transcription of Genes Encoding Enzymes of Oxidative Phosphorylation

Abstract

The energy production of a cell is tuned to its needs. Most of the energy requirements are met by oxidative phosphorylation taking place in the respiratory chain of the mitochondria and approximately 90 % of the oxygen is consumed there. Depending on the challenge, the oxidative capacity can slightly increase or can vary over an order of magnitude, the mitochondria reacting accordingly with either subtle changes in the activity of OXPHOS, with an increased biosynthesis of some of the OXPHOS subunits, or with an increase in the number and size of the organelles (mitogenesis) (Enriquez et al. 1999b, Weber et al. 2002. Therefore, mitochondria are prime targets for regulatory agents affecting ATP yield, and such major regulators of mitochondrial energy metabolism are the steroid and thyroid hormones.This review deals with the role and mechanisms of action of steroid hormones on mitochondria in connection with energy production and their biogenesis. Most of the actions of steroids in this respect affect transcription of OXPHOS genes, the intensity of which parallels the enzymatic activity of the OXPHOS. The OXPHOS represent enzyme proteins composed of several subunits, some of which are encoded in the nuclear and some in the mitochondrial genome. Steroid effects have been documented on mitochondrial gene transcription, without or with parallel involvement of nuclear OXPHOS gene transcription, in a coordinate or not manner, implying the need to consider mechanisms of steroid hormone action on these two distinct organelles and to elaborate on modes of coordination of the nuclear and the mitochondrial transcriptional processes (Scheller et al. 2002).1. Physiological action of steroid hormones on energy metabolism Steroid hormones regulate a wide variety of physiological processes -developmental, growth and metabolic -which require increased energy expenditure. Among the steroid hormones, glucocorticoids play a major role in survival during traumatic stress and injury which require energy (Frayn, 1986;De Feo, 1996). The energy demands depend on the levels of the circulating glucocorticoid, increased concentrations of hormones leading to increased resting energy expenditure (REE) and metabolic rate (Brillon et al. 1995) and to a parallel decrease of the respiratory quotient, suggesting that energy expenditure is fuelled by fatty acid

GR24, a Synthetic Analog of Strigolactones, Stimulates the Mitosis and Growth of the Arbuscular Mycorrhizal FungusGigaspora roseaby Boosting Its Energy Metabolism

“…Strigolactones could also first target mitochondrial or cytoplasmic receptors, as do thyroid hormones in mammalian cells that stimulate mitochondrial biogen- esis, lipid catabolism, and respiration (Scheller and Sekeris, 2003;Weitzel et al, 2003). It was also proposed in the seed of the parasitic Orobanche that strigolactones bind plasmalemma receptors, establishing a covalent link (Humphrey and Beale, 2006).…”

Steroid and thyroid hormone receptors in mitochondria

“…In case, however, this ROS inactivating process is compromised, ROS accumulate with deleterious effects on DNA (mutations) and on other macromolecules, leading to reduced ATP availability and increased oxidative stress, activation of the mitochondrial permeability transition pore and initiation (77). Thus, the regulation of the energetic requirements of the cell is a crucial process, involving a pleiade of agents (22), necessitating a tight coordination of mitochondrial functions with those of other cell compartments (21,22,26,(78)(79)(80)(81).…”

“…The steroid and thyroid hormones also exert rapid effects by way of membrane bound receptors-classical, G-protein associated, or still unidentified molecules (7)(8)(9)(10) resulting in modulation of membrane, cytoplasmic, and/or nuclear associated processes (11). The detection of steroid and TRs in mitochondria of a variety of cells raised the question as to the role of these agents in mitochondrial physiology and in the coordination of processes necessitating the involvement of both nuclear and mitochondrial actions (12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27).…”

Molecular Mechanisms Conferring Resistance/Sensitivity to Glucocorticoid-Induced Apoptosis

“…GR phosphorylation at S226 results in inhibition of the GR function, possibly due to increased GR nuclear export and is a result of JNK activation [80,89,97,98]. Finally, phosphorylation of GR at S404 attenuates GR signalling and is due to GSK3 kinase activation [99]. We have recently reported that differential GR phosphorylation in the resistant CEM-C1-15 versus sensitive CEM-C7-14 ALL cells modulates GR transcriptional activity and target selectivity resulting in diverse pro-or anti-apoptotic Bcl-2 family members' gene expression in the two cell lines [58].…”