In this study, we demonstrate that autophagy plays a critical role in mediating DNA damage response and energetic homeostasis in mouse mIDH1 glioma models and human mIDH1 gliomas co-expressing TP53 and ATRX inactivating mutations.2,15 Through epigenetic, transcriptomic, metabolomic, and signaling pathway analysis, we show that the epigenetic changes in mIDH1 gliomas, with TP53 and ATRX loss of function mutations, modulate the expression of several genes that functionally impact mitochondrial metabolism and upregulate autophagy. Here, TP53 is linked to central nervous system cancer.