Fig. 4.

A model for ‘oncogenic/metastatic licensing’ through mtDNA mutation-derived mitochondrial dysfunction. Although mitochondrial dysfunction can be advantageous to cancer cells, and possibly oncogenic to normal cells, total ablation of mitochondrial function is likely detrimental to both. The genetic and metabolic plasticity afforded to cells bearing heteroplasmic mutations permits greater oncogenic/metastatic potential once a threshold for heteroplasmy-induced mitochondrial dysfunction is reached. A ‘permissive metabolic zone’ of heteroplasmy-induced mitochondrial dysfunction is proposed. Green circles, wild-type mtDNA; red circles, mutant mtDNA