Exercise can be broadly split into two modes; endurance and resistance exercise. Each mode of exercise leads to mode specific adaptations such as increased muscle mass with resistance exercise and improved fatigue resistance with endurance exercise. Data from some animal and ex vivo studies suggested that there were a series of kinase cascades responsive to specific modes responsible for the respective adaptations. For instance, the AMP-activated protein kinase (AMPK) was thought to be specifically responsive to endurance exercise whilst the mammalian target of rapamycin complex 1 (mTORC1) was specifically responsive to resistance exercise and the recurrent activation of each was believed to lead to the respective mode specific adaptations. Later research showed that not only were these pathways not entirely mode specific but that there were other exercise sensitive post translational modifications such as acetylation playing a role in exercise responses. These more recent studies lead us to the question of how does the muscle interpret this degree of signalling noise from multiple inputs and multiple post translational modifications? 14-3-3 proteins act as logic gates in kinase/phosphorylation pathways and as such filter out signalling noise. In particular they bind to substrates when phosphorylated by the AGC (PKB, p90RSK, p70S6K1), CamKK and AMPK family of kinases. Incidentally, members of all of these families are exercise sensitive. 14-3-3s bind to and sequester or change the function of proteins in a target protein phosphorylation dependent manner. Additionally, their function is regulated by their acetylation status. Using running as a model of endurance exercise in mice with or without the histone de-acetylase SIRT1 we are investigating the role of 14-3-3 interaction in the acute response to endurance exercise. In this symposium I will discuss the impact that exercise and loss of SIRT1 have on global 14-3-3 binding and the potential influence this may have on mitochondrial biogenesis.