In conclusion, our data identified a novel mechanism that the hypoxic microenvironment of RCC enhanced p300/CBP-mediated acetylation of ERRα and triggered an increased transcriptional performance of ERRα on the transactivation of LAMP2 and VAMP8, which maintained lysosome-dependent autophagy flux and the fusion of autophagosomes with lysosomes in RCC cells (Figure S8). Here, VAMP8 is linked to renal cell carcinoma.