Nutrient deprivation induces a number of physiological responses, including autophagy. This evolutionarily conserved process allows breakdown and recycling of cellular components and is regulated by the ATG genes in yeast and their orthologs in higher organisms. However, the transcriptional control of these genes is still incompletely understood. In a screen to identify factors regulating ATG gene expression upon nitrogen starvation, Klionsky and colleagues have now identified Rph1 as a transcriptional repressor of a subset of ATG genes under nutrient-replete conditions. Rph1 is a histone demethylase that acts to reverse methylation of Lys36 of histone H3. However, the demethylase activity of Rph1 is dispensable for the autophagic response, although promoters of Rph1-responsive ATG genes contain Rph1-binding sites. Zinc-finger motifs in Rph1 were found to interact with these sites in the ATG7 promoter and were required for Rph1's ability to inhibit autophagy, thus suggesting that DNA binding mediates Rph1's function as a transcriptional repressor. Nitrogen starvation led to decreased levels of Rph1 protein and induced its phosphorylation. Rim15, a kinase that integrates signals from various nutrient-sensing pathways, was shown to mediate Rph1 phosphorylation in this context. Knockdown experiments in HeLa cells demonstrated that KDM4A, a mammalian Rph1 homolog, was similarly involved in repressing transcription of certain Atg genes. KDM4A knockdown also led to an increase in several autophagic markers. In addition, autophagy induced by the mTOR inhibitor Torin1 resulted in phosphorylation of KDM4A and reduced its cellular levels. Together, these results suggest that Rph1's function is evolutionarily conserved. Although Rph1 had previously been implicated in nutrient signaling, the current study defines its role in repressing autophagy-related genes under nutrient-rich conditions and provides insights into the signal-transduction pathway linking nutrient sensing and Rph1-mediated regulation of autophagy. (Curr. Biol. 25, 546–555, 2015)