Introduction: In order to maintain metabolic homeostasis, organisms adjust the capacity and efficiency of ATP generation to changes in energetic demand and supply. While the transcriptional control of mitochondrial biogenesis allows to adapt mitochondrial respiratory capacity with long-term requirements for differential energy demand (e.g.: exercise training), bioenergetic adaptation also needs to take place within shorter time frames in order to properly fine-tune nutrient availability, energy production and demand, either in a circadian fashion or after a meal. These quick metabolic responses can be achieved through exquisite modulation of diverse post-translational modifications, which influence a variety of mitochondrial processes, including mitochondrial dynamics, fatty acid oxidation, lipogenesis and bioenergetic efficiency. Conclusion: In this review, we will specially focus on the role of mitochondrial sirtuin enzymes as modulators of mitochondrial ac(et) ylation and the possible interactions with other posttranslational modification events.