TFAM depletion overcomes hepatocellular carcinoma resistance to doxorubicin and sorafenib through AMPK activation and mitochondrial dysfunction.

•TFAM upregulation is not a persistent molecular characteristic in HCC.•TFAM is upregulated in doxorubicin and sorafenib resistant HCC cells.•TFAM depletion inhibits HCC growth and survival but not migration.•HCC resistant cells have increased mitochondrial biogenesis.•TFAM inhibition leads to AMPK activation and mitochondrial dysfunction.