Adenoviral overexpression of DN-KLHL3 in the primary hepatocytes of mice and human hepatoma cells enhanced the OCR and ECAR; however, WT-KLHL3 overexpression in hepatocytes showed similar levels of the OCR and ECAR compared to those of Ad-GFP controls, suggesting that DN-KLHL3 could specifically regulate mitochondrial function in hepatocytes. Here, KLHL3 is linked to hepatocellular carcinoma.