**3.1 The physiological importance of compartmentalization of glutathione**

Pioneer work from Meister, (Meister & Anderson, 1983) correlated GSH synthesis and its degradation throughout the so-called -glutamyl cycle, and defined it as a cytosolic processes. The importance of cellular compartmentalization of GSH is two fold, first because it plays an important role in fighting against radical oxygen species (ROS). It is well known that these molecules have a very short half life and exert their action close to the place they were produced. Thus, the presence or absence of GSH could determine the development of localized oxidative damage for the cell structure or metabolic function developed in the vicinity. Secondly, GSH compartmentalization is of vital importance because of its role as a cellular detoxifying agent; it is known that tumours that have high glutathione levels are more resistant to chemotherapy, and the importance of nuclear (Voheringer et al., 1998) and mitochondrial (Benlloch et al. 2005) compartmentalization of GSH has been pointed out.

The overview of compartmentalization of glutathione in mammal cells is a complicated matter. This is due to the presence in the literature of a number of contradictory reports. The reason for the controversy is mainly methodological. Until very recently most reports were mainly based on cell-fractionation techniques. Those techniques appear to be reliable for mitochondrial studies; however their usefulness in nuclear or even endoplasmic reticulum measurements is at least controversial.
