Liver cancer is one of the most common and lethal types of oncological disease in the world, with limited treatment options. New treatment modalities are desperately needed, but their development is hampered by a lack of insight into the underlying molecular mechanisms of disease. It is clear that metabolic reprogramming in mitochondrial function is intimately linked to the liver cancer process, prompting the possibility to explore mitochondrial biochemistry as a potential therapeutic target. Here we report that depletion of mitochondrial DNA, pharmacologic inhibition of mitochondrial electron transport chain (mETC) complex I/complex III, or genetic of mETC complex I restricts cancer cell growth and clonogenicity in various preclinical models of liver cancer, including cell lines, mouse liver organoids, and murine xenografts. The restriction is linked to the production of reactive oxygen species, apoptosis induction and reduced ATP generation. As a result, our findings suggest that the mETC compartment of mitochondria could be a potential therapeutic target in liver cancer.
Bibliographical noteFunding Information:
This research is supported by a KWF Young Investigator Grant (No. 10140) from the Dutch Cancer Society and a VIDI grant (No. 91719300) from the Netherlands Organization for Scientific Research (NWO) to Q. Pan. This research is also financially supported by the China Scholarship Council Ph.D. fellowship (File No. 201506100033) to ML and LW (File No. 201708530248).
© 2021, The Author(s).