Role and mechanism of mitochondrial deoxyguanosine kinase in lung cancer tumorigenesis

Deletion or mutation of mitochondrial deoxyguanosine kinase ( dguok ) is a major cause of mitochondrial DNA deletion syndrome. However, the role and mechanism of dguok in tumorigenesis have not been documented. We found that deletion of dguok in lung cancer H1650 cells reduced the Sphere formation, an indicator of cancer stem cell growth. dguok deletion not only caused the morphological changes of mitochondria, but also dramatically decreased the oxygen consumption rate (OCR). Although dguok deletion reduced the number of mitochondrial DNA copies, it did not significantly reduce the mRNA level of mitochondrial DNA-coding genes. Further analysis showed that dguok deletion considerably lowered the protein level of NDUFB8, a component of mitochondrial complex I, but did not affect the mRNA level of ndufb8 . These findings suggested that dguok affected mitochondrial function and tumorigenesis through regulation of mitochondrial complex I level.