On mitochondrial metabolism in tumor biology

To provide examples of mitochondria-specific metabolic events that influence tumor cell biology, and of metabolism-related mitochondrial biomarkers and therapeutic targets in cancer cells.

Cancer cell mitochondria are rewired to optimally serve the cancer cell under various conditions of cellular stress. The nonexhaustive list of mitochondrial alterations that support cancer cell proliferation, survival, and/or progression includes upregulation of oxidative metabolism and use of alternative substrates, oncometabolites, increased superoxide production, mutated mitochondrial DNA, and altered mitochondrial morphology and dynamics. Potential therapeutic targets include fatty acid oxidation, voltage-dependent anion channel-1, the pyruvate dehydrogenase complex, and Complex I.

Some phenotypical traits, for example, chemoresistance and metastasis, are likely regulated by a fine-tuned balance between several metabolic processes and events that are upregulated in parallel and are also dependent on microenvironmental cues. Many metabolism-related mitochondrial biomarkers show prognostic value, but the biological interpretation of the data may be confounded by the overall metabolic status and context. Understanding metabolic regulation of stemness is important for targeting cancer stem cells. Therapeutic targeting of cancer cell mitochondria remains experimental but promising, and more predictive markers will be needed for metabolism-based treatments and personalized medicine.