Over the past few years it has become clear that mitochondria are not merely the powerhouses of cells. Proteome-analyses of mitochondria from different organisms and organs revealed that more than 1000 proteins are localized in and/or on mitochondria. This by far exceeds the number of proteins required for classical mitochondrial functions, e.g. the respiratory chain, the tricarboxylic acid cycle, fatty acid oxidation and apoptosis. This suggests that many of these proteins have other, as yet unknown functions. Several proteins with well-described nuclear functions, like the transcription factor FoxO3A or the Telomerase Reverse Transcriptase, have recently been shown to be localized also within the mitochondria. This mini-review will focus on the description of the functions of these two proteins in the nucleus and in the mitochondria - as two examples of many more proteins, which are yet to be uncovered. It will give insights into the role of these proteins within different organelles of the cell and will reveal that the functions of the proteins are probably not the same in the nucleus and the mitochondria. Therefore, these differences have to be considered when targeting proteins for therapeutic approaches.