Copper is essential for all living organisms but is toxic when present in excess. Therefore organisms have developed homeostatic mechanism to tightly regulate its cellular concentration. In a recent study we have shown that CopRS two-component system is essential for copper resistance in the cyanobacterium Synechocystis sp PCC 6803. This two-component regulates expression of a heavy-metal RND type copper efflux system (encoded by copBAC) as well as its own expression (in the copMRS operon) in response to an excess of copper in the media. We have also observed that both operons are induced under condition that reduces the photosynthetic electron flow and this induction depends on the presence of the copper-protein, plastocyanin. These findings, together with CopS localization to the thylakoid membrane and its periplasmic domain being able to bind copper directly, suggest that CopS could be involved in copper detection in both the periplasm and the thylakoid lumen.