Fig. 7: Inhibition of Drp1 or supplement with fumarate prolongs lifespan of mice with dilated cardiomyopathy.

a–c TEM analysis for left ventricles of hearts from WT, Sdhaf4 mutant mice, mutant mice with fumarate or Mdivi-1 supplement for 4 weeks, representative images (a, scale bar, 1 μm and 200 nm respectively), mitochondrial number per section (b, n = 3, P < 0.0001), average mitochondrial area (c, n = 293 for WT, n = 650 for mutants, n = 305 for fumarate, n = 230 for Mdivi-1, P < 0.0001). d Relative expression of hypertrophic and fibrotic-associated genes in left ventricle of hearts of mice (n = 8, P < 0.0001). e–j Heart function measurements of WT, Sdhaf4 mutants, Sdhaf4 mutant mice with fumarate or Mdivi-1 supplement for 4 weeks: EF (e, P < 0.0001, P = 0.012), corrected LV mass (f, P < 0.0001), LVID-s (g, P < 0.0001), FS (h, P < 0.0001), LVESV (i, P < 0.0001), and LVEDV (j, P < 0.0001, P = 0.011), n = 8. k Postnatal survival curve for WT (n = 25 for both sex), Sdhaf4 mutant mice (n = 60 for both sex), Sdhaf4 mutant mice with daily fumarate supplement (n = 18 for both sex) and Sdhaf4 mutant mice with daily Mdivi-1 supplement (n = 18 for both sex), P < 0.0001. Values are mean ± SEM, *P < 0.05, **P < 0.01. Statistical significance was determined by two-tailed Student’s t-test (b–j). Log-rank Mantel-Cox testing was performed for survival analysis (k). Source data are provided in Source Data file. EF ejection fraction, LV left ventricular, LVID-s left ventricular internal dimension end-systolic, FS fraction shortening, LVESV left ventricular end-systolic volume, LVEDV left ventricular end- systolic volume.