Electrostatic Association of Glutathione Transferase to the Nuclear Membrane

Abstract

The possible nuclear compartmentalization of glutathione S-transferase (GST) isoenzymes has been the subject of contra dictory reports. The discovery that the dinitrosyl-diglutathio nyl-iron complex binds tightly to Alpha class GSTs in rat hepa tocytes and that a significant part of the bound complex is also associated with the nuclear fraction (Pedersen, J. Z., De Maria, F., Turella, P., Federici, G., Mattei, M., Fabrini, R., Dawood, K. F., Massimi, M., Caccuri, A. M., and Ricci, G. (2007) J. Biol. Chem. 282, 6364– 6371) prompted us to reconsider the nuclear localization of GSTs in these cells. Surprisingly, we found that a considerable amount of GSTs corresponding to 10% of the cyto solic pool is electrostatically associated with the outer nuclear membrane, and a similar quantity is compartmentalized inside the nucleus. Mainly Alpha class GSTs, in particular GSTA1-1, GSTA2-2, and GSTA3-3, are involved in this double modality of interaction. Confocal microscopy, immunofluorescence exper iments, and molecular modeling have been used to detail the electrostatic association in hepatocytes and liposomes. A quan titative analysis of the membrane-bound Alpha GSTs suggests the existence of a multilayer assembly of these enzymes at the outer nuclear envelope that could represent an amazing novelty in cell physiology. The interception of potentially noxious com pounds to prevent DNA damage could be the possible physio logical role of the perinuclear and intranuclear localization of Alpha GSTs.