They act in various electron transport systems as functional analogs of Fds. Despite the fact that they have been found only in bacteria and algae, they share similarity with a number of protein domains of both prokaryote and eukaryote origin. In cyanobacteria and enterobacteria, Fld levels increase several fold on exposure to MV and other superoxide -propagating compounds, and overexpression of the flavoprotein in E. coli leads to augmented tolerance toward various sources of oxidative stress. In transgenic tobacco plants, expressing Anabaena Fld in a constitutive fashion, this protein has exerted a notable protection against photo-oxidative and hydric stresses. As in the case of FNR, Fld seems a good candidate for exploration of its protective antioxidative properties in new systems as R428 Axl inhibitor mammalian cells are. In this work we attempted the evaluation of the capacity of P. sativum FNR and Anabaena PCC 7119 Fld to protect Cos-7 cells from oxidative stress challenges in vitro. We found that both FNR and Fld protected against hydrogen peroxide after 24 hours of exposure. Surprisingly, we did not observe protection towards MV by neither of these transgenic proteins. These results reveal antioxidant functions of plant FNR and cyanobacterial Fld in a mammalian cell line opening the opportunity to examine a myriad of applications in diseases where reactive oxygen species are know to play a role in etiology and other clinical situations such as transplantation where the involvement of ROS in primary organ failure has been recognized. Previous work performed by various groups demonstrated the successful interactions and electron transfer of the components of hybrid systems as Anabaena FNR and bovine adrenodoxin and bovine adrenodoxin reductase and Anabaena PCC 7119 Fld. It was also shown that NADPH-Fld reductase/Fld from E. coli can function as electron donors to bovine P450c17 to the same proportional extent as does P450 reductase. NADPH-cytochrome P-450 oxidoreductase gene has most probably arisen through the fusion of the ancestral genes of Fld and FNR. All these evidences prompted us to undertake the present work to test the hypothesis that heterologous proteins originating from plant and cyanobacteria would still be functional in Cos-7 cells. Both proteins were directed to mitochondria via the fusion to their sequence of a MLS of mouse ferredoxin reductase. A number of works reported that proteins can be successfully directed to mitochondria by just fusing their N-terminal ends to a MLS. Mouse Fdxr MLS was recognized by Cos-7 cells where it effectively directed both FNR and Fld to mitochondria. For FNR the MLS seems to be processed correctly as shown by WB analysis were we found a major band corresponding to the size of the mature protein and with only a small proportion remaining as the full-length, non-processed form. This can be explained taking into account that Fld does not posses a localization signal in its native form while pea FNR complete gene bears a chloroplast localization.