This paper deals with the problem of cost-optimal operation of smart buildings that integrate a centralized HVAC system, photovoltaic generation and both thermal and electrical storage devices. Building participation in a Demand-Response program is also considered. The proposed solution is based on a specialized Model Predictive Control strategy to optimally manage the HVAC system and the storage devices under thermal comfort and technological constraints. The related optimization problems turn out to be computationally appealing, even for large-scale problem instances. Performance evaluation, also in the presence of uncertainties and disturbances, is carried out using a realistic simulation framework.