Catalyst deactivation mechanisms on MgO-supported Au(6) clusters are studied for the CO oxidation reaction via first-principle kinetic Monte Carlo simulations and shown to depend on support vacancies. In defect-poor MgO or in the presence of a Mg vacancy, O(2) does not bind to the clusters and the catalyst is poisoned by CO. On Au clusters interacting with O vacancies of the support, O(2) can be chemisorbed and transient activity is observed. In this case, an unexpected catalyst "breathing" mechanism (restructuring) leads to carbonate formation and catalyst deactivation, rationalizing several experimental observations. Our study underscores the importance of the cluster's charge state and dynamics on catalytic activity.