Estrogens have antioxidant properties which are due to their ability to bind to estrogen receptors and to up-regulate the expression of antioxidant enzymes via intracellular signalling pathways. Mitochondria are key organelles in the development of age-associated cellular damage. Recently, estrogen receptors were identified in mitochondria. The aim of this study was to test whether estradiol directly affects highly purified mitochondria by preventing oxidative stress and protecting frail mitochondria.

Incubation with estradiol at normal intracellular concentrations prevents the formation of reactive oxygen species by mitochondria in a saturable manner. This effect is maintained when mitochondria are incubated with estradiol covalently-bound to bovine serum albumin, thus indicating that the hormone binds to mitochondrial membrane receptors. Moreover, estradiol protects mitochondrial integrity as indicated by an increase in mitochondrial membrane potential. It also prevents the apoptogenic leakage of cytochrome c from mitochondria and as a result the mitochondrial content of this cytochrome c is maintained high. Thus, estradiol prevents the onset of the mitochondrial pathway of apoptosis by a direct effect on the organelle. Genistein, a phytoestrogen present at high concentration in soy, mimics the protective effect of estradiol by both decreasing the rate of formation of reactive oxygen species and preventing the release of cytochrome c from mitochondria.

This work has been supported by BFU2007-65803/BFI and ISCIII2006-RED13-027 from the 'Red Temática de investigación cooperativa en envejecimiento y fragilidad' (RETICEF RD06/003–027) to J.V., by grant GV/2007/263 to C.B and by grants GVPRE/2008/138 and Catholic University 2008-011-002 to J. G.