Inhibition of DRP1 rescues mtDNA copy number defect in mfn1−/− MEFs. (a) mfn1−/− MEFs have decreased mtDNA copy number relative to wildtype (WT) cells. ***p < 0.001, unpaired t-test (n = 6). (b) Transiently expressing Drp1K38A-mCherry rescues mtDNA copy number defect in mfn1−/− MEFs. *p < 0.05, unpaired t-test (n = 3). (c) Two active 1H-pyrrole-2-carboxamide compounds, 4 and 7, rescue mtDNA copy number defect in mfn1−/− MEFs in dose-dependent fashion, while an inactive compound from the same scaffold, 11, does not. ****p < 0.0001, ***p < 0.001, *p < 0.05, one-way ANOVA followed by Dunnett’s test vs. 0.1% DMSO (n = 4).