Blocking Mitochondrial Cleanup Helps Survival and Energy Function in MYC-driven Liver Cancer

Hepatocellular carcinomas (HCC) driven by the MYC gene show significant reductions in oxidative phosphorylation (OXPHOS) and TCA cycle activity.

• MYC-driven HCC tumors exhibit decreased expression of genes encoded by mitochondrial DNA while showing increased expression of nuclear-encoded mitochondrial genes.
• Analysis of murine models of MYC- and CTNNB1-driven HCC reveals aberrant mitochondrial metabolism in all cases.
• Increased levels of reactive oxygen species (ROS) are associated with reduced OXPHOS and TCA cycle activity in MYC-driven tumors.
• MYC's role includes inducing the expression of nuclear respiratory factor 1 (NRF1), which regulates genes that promote mitophagy.
• Knocking out the DRP1 gene leads to reduced mitophagy and ROS levels, enhancing the survival of mice with HCC.

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