--- res: bibo_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 NDUFA10E160A/R161A shows reduced dGTP binding capacity in vitro and leads to a 50% reduction in mitochondrial dGTP content, proving that most dGTP is directly bound to the dNK domain of NDUFA10. This interaction may represent a hitherto unknown mechanism regulating mitochondrial dNTP availability and linking oxidative metabolism to DNA maintenance.@eng bibo_authorlist: - foaf_Person: foaf_givenName: David foaf_name: Molina-Granada, David foaf_surname: Molina-Granada - foaf_Person: foaf_givenName: Emiliano foaf_name: González-Vioque, Emiliano foaf_surname: González-Vioque - foaf_Person: foaf_givenName: Marris G. foaf_name: Dibley, Marris G. foaf_surname: Dibley - foaf_Person: foaf_givenName: Raquel foaf_name: Cabrera-Pérez, Raquel foaf_surname: Cabrera-Pérez - foaf_Person: foaf_givenName: Antoni foaf_name: Vallbona-Garcia, Antoni foaf_surname: Vallbona-Garcia - foaf_Person: foaf_givenName: Javier foaf_name: Torres-Torronteras, Javier foaf_surname: Torres-Torronteras - foaf_Person: foaf_givenName: Leonid A foaf_name: Sazanov, Leonid A foaf_surname: Sazanov foaf_workInfoHomepage: http://www.librecat.org/personId=338D39FE-F248-11E8-B48F-1D18A9856A87 orcid: 0000-0002-0977-7989 - foaf_Person: foaf_givenName: Michael T. foaf_name: Ryan, Michael T. foaf_surname: Ryan - foaf_Person: foaf_givenName: Yolanda foaf_name: Cámara, Yolanda foaf_surname: Cámara - foaf_Person: foaf_givenName: Ramon foaf_name: Martí, Ramon foaf_surname: Martí bibo_doi: 10.1038/s42003-022-03568-6 bibo_issue: '1' bibo_volume: 5 dct_date: 2022^xs_gYear dct_identifier: - UT:000815098500002 dct_isPartOf: - http://id.crossref.org/issn/23993642 dct_language: eng dct_publisher: Springer Nature@ dct_title: Most mitochondrial dGTP is tightly bound to respiratory complex I through the NDUFA10 subunit@ fabio_hasPubmedId: ' 35739187' ...