Mitochondrial Dna Mutations Drive Cancer Initiation: New Study Reveals Mt-Nd5 Role

In a groundbreaking study, Dr. Zhenglong Gu and his team at Fudan University have discovered that heteroplasmic mutations in the mitochondrial gene MT-ND5 are critical drivers of cancer initiation. The research, published in Mitochondrial Communications, demonstrates how these mutations disrupt oxidative phosphorylation and promote oncogenic transformation. This finding challenges the traditional view that primarily emphasizes nuclear genomic alterations as the main cause of cancer. The study introduced de novo mutations into the MT-ND5 gene, creating cellular models mimicking heteroplasmy. Results showed that even low to moderate levels of MT-ND5 mutations impair complex I activity, leading to increased mitochondrial reactive oxygen species (ROS). This oxidative stress significantly heightens the cells' oncogenic potential. The metabolic rewiring associated with MT-ND5 heteroplasmy involves a shift from oxidative phosphorylation to glycolysis, aligning with the Warburg effect. However, the shift primarily restores NAD+ pools, essential cofactors in metabolic pathways. This research highlights the mitochondrial genome's role in cancer initiation, paving the way for personalized cancer prevention and prediction.