Mitochondrial deoxyribonucleotide pools in deoxyguanosine kinase deficiency

Molecular Genetics and Metabolism
Ann Saada

Abstract

Mutated deoxyguanosine kinase (dGK), which catalyses the first step of the mitochondrial deoxypurine salvage pathway, accounts for a hepatocerebral variant of mitochondrial DNA (mtDNA) depletion syndromes. In order to elucidate the pathogenic mechanism of dGK deficiency, mitochondrial and cytoplasmic deoxyribonucleoside triphosphate (dNTP) pools in cycling and quiescent fibroblasts from a dGK deficient patient were measured. The mitochondrial dNTP pools were found to be imbalanced, mainly in quiescent cells due to decreased dGTP while mtDNA content and mitochondrial respiratory chain activities were concomitantly decreased. Supplementation of deoxyguanosine and deoxyadenosine normalized mitochondrial dNTP pools, mtDNA content and partially restored the MRC function. It is suggested that the cytoplasmic deoxycytine kinase supplemented with external substrates may compensate for the deficient dGK.

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Citations

Dec 3, 2014·Molecular Genetics and Metabolism·Mauro ScarpelliMassimiliano Filosto
Jun 15, 2010·Nucleosides, Nucleotides & Nucleic Acids·L Wang
Apr 30, 2015·International Journal of Molecular Sciences·Michael Fasullo, Lauren Endres
Jul 3, 2013·Drug Discovery Today·Yolanda CámaraRamon Martí
Mar 5, 2015·Cell Metabolism·Arnaud BessePenelope E Bonnen
Aug 25, 2009·The Biochemical Journal·Ann Saada
Jan 15, 2014·The International Journal of Biochemistry & Cell Biology·Ann Saada
May 23, 2012·Molecular Genetics and Metabolism·Stefanie BulstRita Horvath
Dec 17, 2009·Neurochemistry International·Marcella CamiciMaria Grazia Tozzi
Jan 14, 2016·PLoS Genetics·Ilaria Dalla RosaAntonella Spinazzola
Nov 15, 2018·Human Molecular Genetics·Benjamin MunroJuliane S Müller
Mar 9, 2019·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Cora Blázquez-BermejoYolanda Cámara
Dec 29, 2020·Journal of Inherited Metabolic Disease·Mark A Vanden AvondMichael W Lawlor
Dec 18, 2021·Acta Neuropathologica·Jo M VanoevelenConstance T R M Stumpel

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