Regulation of mitochondrial respiratory chain structure and function by estrogens/estrogen receptors and potential physiological/pathophysiological implications

Abstract

It is well known that the biological and carcinogenic effects of 17beta-estradiol (E2) are mediated via nuclear estrogen receptors (ERs) by regulating nuclear gene expression. Several rapid, non-nuclear genomic effects of E2 are mediated via plasma membrane-bound ERs. In addition, there is accumulating evidence suggesting that mitochondria are also important targets for the action of estrogens and ERs. This review summarized the studies on the effects of estrogens via ERs on mitochondrial structure and function. The potential physiological and pathophysiological implications of deficiency and/or overabundance of these E2/ER-mediated mitochondrial effects in stimulation of cell proliferation, inhibition of apoptosis, E2-mediated cardiovascular and neuroprotective effects in target cells are also discussed.

Estrogen actions on mitochondria—Physiological and pathological implications

“…Consistently, extranuclear localization of both ERα and ERβ has been indicated Milner et al, 2005;Herrick et al, 2006). In fact, increasing evidence has demonstrated that ERβ are mainly localized extranuclearly Cammarata et al, 2004;Chen et al, 2004a;Yang et al, 2004;Chen et al, 2005;Herrick et al, 2006). (Gustafsson, 1999).…”

“…In recently years, estrogens have been appreciated as pleiotropic hormones that play roles in a wide variety of nonreproductive functions as cardiovascular function (Stevenson, 2000), memory and cognition (Sherwin, 1999), bone and mineral metabolism (Compston, 2001), and immune function (Ahmed et al, 1999). As indicated above, there is accumulating evidence suggesting that mitochondria are also important targets for the actions of estrogens (Chen et al, 2005;Felty and Roy, 2005)). Mitochondria play a fundamental role in cell respiration, through oxidative phosphorylation.…”

“…Hence, it is not surprising that ERβ has very low classic transcriptional activity, when compared with ERα (Lubahn et al, 1993;Cowley et al, 1997;Pettersson et al, 1997;Ogawa et al, 1998;Cowley and Parker, 1999;Curtis et al, 2000;Yi et al, 2002). There is accumulating evidence suggesting that mitochondria are also important targets for the actions of estrogens (Chen et al, 2005;Felty and Roy, 2005). Mitochondria play a fundamental role in cell respiration and oxidative phosphorylation.…”

Nuclear receptors, mitochondria and lipid metabolism

“…The first receptors to be cloned, the endocrine nuclear hormone receptors, were discovered in an effort to define the mechanism of action of known hormones, such as: the amino-acid-derived thyroid hormone; the steroidal glucocorticoid, mineralocorticoid, and sex hormones; and the vitamins A and D. Several of these endocrine receptors, e.g. thyroid (TR), estrogen, (ER) and Vitamin D (VDR) receptors have established or emerging roles for influencing metabolic and mitochondrial function, reviewed elsewhere (Weitzel et al 2003;Chen et al 2005;Roy et al 2007). Subsequent to the molecular identification of classical endocrine receptors, additional members of the nuclear hormone receptor superfamily, so called "adopted orphan receptors", were discovered to respond with low-affinity to physiologic ligands derived from dietary and metabolic sources, such as bile salts, fatty acids and eicasanoids, present in concentrations (micromolar) orders of magnitude higher than classic endocrine hormones (nanomolar).…”

Spatial Distribution of Cellular Function: The Partitioning of Proteins between Mitochondria and the Nucleus in MCF7 Breast Cancer Cells

“…24 The mitochondrial genome encodes only 13 proteins that are part of the oxidative-phosphorylation complexes I, III, IV and V of the mitochondrial inner membrane. 25 Since most mitochondrial proteins are nuclear encoded, mechanisms for the biogenesis of mitochondria, the coordination of mitochondrial biogenesis with the cell cycle and the establishment/maintenance of the mitochondrial proteome have been intensively investigated. [26][27][28][29] Several mechanisms for protein trafficking involving mitochondria are known.…”