Significance Autophagy allows the lysosomal degradation of intracellular material. It is a tightly regulated process controlled by the tumor-suppressor gene p53, among others. Here we report a unique regulator of autophagy, BAT3, which modulates the intracellular localization of the enzyme p300, an enzyme that adds some acetyl residues on targets proteins (acetylation) to modulate their activity. To stimulate autophagy, BAT3 allows the acetylation of p53 by p300 in the nucleus, but limits the p300-dependent acetylation of ATG7, a protein specific for autophagy, in the cytosol. Thus, BAT3 acts on both the cytosol and the nucleus to tightly modulate autophagy.