MPV17 is upregulated in non-dividing cells and quiescence induces mtDNA depletion in MPV17-deficient human fibroblasts, unless supplemented with deoxynucleosides.

<p><b>(A)</b> Steady state levels of MPV17 protein in proliferating and quiescent control fibroblasts. (<b>B</b>) Relative mtDNA levels in proliferating control (black) and MPV1<i>7</i> mutant fibroblasts (gray). (<b>C</b>) MtDNA quantification in quiescent fibroblasts. The mtDNA amount is expressed relative to the mean of the controls. (<b>D</b>) mtDNA copy number of quiescent control and MPV17-mutant fibroblasts. Data are expressed as mean ± SEM of n = 8. (Student’s t test: ***P<0.001). (<b>E</b>) Mitochondrial dNTP levels in quiescent control and MPV17-mutant fibroblasts. dATP levels were disregarded owing to the low values obtained for the controls. dCTP and dGTP were measured in 3 independent experiments in 3 patients and 3 control cell lines. *** P<0.001—Mann-Whitney test. (<b>F)</b> Relative mtDNA copy number in quiescent fibroblasts supplemented with deoxynucleosides. Quiescent fibroblasts were cultured for 14 days in the absence or presence of 50 μM or 100 μM deoxyadenosine (AdR), deoxycytosine (CdR), deoxyguanosine (GdR), deoxythymidine (TdR) alone or in the different combinations as indicated. The amount of mtDNA is expressed relative to its amount in proliferating cells (Student’s t test: *P<0.05; **P<0.01; ***P<0.001); C1 and C2, control fibroblasts; P1-P5, fibroblasts derived from patients with pathological mutations in <i>MPV17</i> (<a href="" target="_blank">S2 Table</a>).</p>