Most mitochondrial dGTP is tightly bound to respiratory complex I through the NDUFA10 subunit.

ABSTRACT: Imbalanced mitochondrial dNTP pools are known players in the pathogenesis of multiple human diseases. Here we show that, even under physiological conditions, dGTP is largely overrepresented among other dNTPs in mitochondria of mouse tissues and human cultured cells. In addition, a vast majority of mitochondrial dGTP is tightly bound to NDUFA10, an accessory subunit of complex I of the mitochondrial respiratory chain. NDUFA10 shares a deoxyribonucleoside kinase (dNK) domain with deoxyribonucleoside kinases in the nucleotide salvage pathway, though no specific function beyond stabilizing the complex I holoenzyme has been described for this subunit. We mutated the dNK domain of NDUFA10 in human HEK-293T cells while preserving complex I assembly and activity. The NDUFA10^E160A/R161A

SUBMITTER: Molina-Granada D 

PROVIDER: S-EPMC9226000 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature