Disturbed mitochondrial acetylation in accordance with the availability of acetyl groups in hepatocellular carcinoma.

As an essential post-translational modification, acetylation participates in various cellular processes and shows aberrances during tumorigenesis. Owing to its modification substrate, acetyl-CoA, acetylation is postulated as a depot for acetyl groups and evolve to build a connection between epigenetics and metabolism. Here we depict a distinct acetylome atlas of hepatocellular carcinoma from the perspectives of both protein acetylation and acetyl-CoA metabolism. We found that tumor acetylome demonstrated a compartment-dependent alteration that the acetylation level of mitochondrial proteins tended to be decreased while nuclear proteins were highly acetylated. In addition, elevated expression of ATP-citrate synthase (ACLY) was observed in tumors, which would facilitate histone acetylation by transporting mitochondrial acetyl coenzyme A to the nucleus. A hypothetical model of the oncogenic acetylome was proposed that growing demands for histone acetylation in tumor cells would drive the relocalization of acetyl-CoA to the nucleus, which may contribute to the global deacetylation of mitochondrial proteins to support the nuclear acetyl-CoA pool in an ACLY-dependent manner. Our findings are thought-provoking on the potential linkage between epigenetics and metabolism in the progression of tumorigenesis.