Lung adenocarcinoma (LUAD) is a common and very aggressive cancer. Recent studies suggest that LUAD is highly dependent on mitochondrial function, as it relies more on mitochondrial DNA (mtDNA) expression than other cancers. By using powerful genetic models that allow the modulation of mitochondrial DNA levels and the expression of the oncogenic Kras allele, we discovered a novel specific role for mtDNA in lung tumor progression. Our previous data show that increasing mtDNA levels is sufficient to aggravate tumor burden in mice, whereas depleting mtDNA has a protective effect. We also found that high mtDNA levels confer increased mitochondrial respiration potential and enhance electron flux through complex I. We now aim to understand the cellular pathways and mechanism behind this effect.