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Heteroplasmic de novo MT-ND5 Truncating Mutations: Implications for Mitochondrial Function in Oncogenesis

With mitochondrial DNA (mtDNA) base editing tools, this study controlled the nuclear background to investigate the causal effect of mtDNA mutations. Co-existence of wild-type and mutant mtDNA (heteroplasmy) in MT-ND5 was introduced. Enhanced oncogenic potential was confirmed with in vitro and in vivo assays. They reported compromised mitochondrial respiration and increased glycolytic activity, often termed as the Warburg effect following the mutations. By tracking cellular phenotypes during the MT-ND5 heteroplasmy decay, they reasoned that the increased glycolytic activity was to rescue NAD+ depreciation. Increased ROS level, genome instability, altered NAD+ epigenetics are the likely factors drove oncogenesis post MT-ND5 mutations.

May 19, 2025