Fig. 1: Mitochondrial CaMKII is activated by MI and causes dilated cardiomyopathy.

a Western blot of mitochondrial lysates and b summary data for phosphorylated CaMKII and total CaMKII and phosphorylated MCU and total MCU normalized to Coomassie staining in mitochondrial from sham (n = 7) and MI (n = 8) hearts. Blots for cellular compartment markers also included: SERCA2a (SR membrane), PDH (mitochondrial matrix), GAPDH (cytosol). c Summary data from echocardiographic measurements from WT and mtCaMKIIN mice before (WT n = 12, mtCaMKIIN n = 16), 1 (WT n = 12, mtCaMKIIN n = 16) and 3 weeks (WT n = 6, mtCaMKIIN n = 7) after MI. EF (left ventricular ejection fraction), EDV (left ventricular end-diastolic volume), ESV (left ventricular end-systolic volume). d Schematic of the mtCaMKII transgene construct, α-MHC: α-myosin heavy chain, cox8a: cox8a mitochondrial localization sequence, Flag: flag epitope tag, HGH1 polyA: human growth hormone polyA signal. e Immunofluorescence micrographs of isolated ventricular myocytes from WT and mtCaMKII mice. This experiment was repeated independently twice with similar results. f Representative echocardiographic images in end diastole, LV: left ventricle, Ao: aorta. g Summary data for echocardiographic measurements from adult WT (n = 20 EF, EDV, ESV; n = 13 LVWT; n = 16 HW/BW) and mtCaMKII (n = 23 EF, EDV, ESV; n = 13 LVWT; n = 22 HW/BW) mice. LVWT (left ventricular wall thickness), HW/BW (heart weight/body weight). h Summary data for echocardiographic measurements from young (1–6 weeks of age) WT (n = 12) and mtCaMKII (n = 6) mice. i Representative transmission electron micrographs from WT and mtCaMKII left ventricle. j Mitochondrial injury score for WT (n = 6) and mtCaMKII (n = 6) hearts. k Mitochondrial DNA content (cox1) normalized to nuclear DNA (βglobin) for WT (n = 4) and mtCaMKII (n = 4) hearts. l Kaplan–Meier survival relationship for WT (n = 41) and mtCaMKII (n = 48) mice. Data are represented as mean ± SEM, significance was determined using a two-tailed Student’s t test or log-rank test (survivorship). ****P < 0.0001, ***P < 0.001, **P < 0.01, *P < 0.05, NS = not significant. Source data, including exact p values, are provided as a Source data file.