Downregulation of FUNDC1/MAMs/CREB/Fis1 signaling in human heart failure patients. A, The protein levels of FUNDC1, inositol 1, 4, 5-trisphosphate type 1 receptor (IP3R1), inositol 1, 4, 5-trisphosphate type 3 receptor (IP3R3), phosphorylated cAMP response element binding protein (pCREB), and mitochondrial fission 1 protein (Fis1) in human heart specimens from donor or heart failure patients were determined by western blot. B, Densitometric analysis of the protein levels in A (mean ± SD, n = 4; *P < 0.05, **P < 0.01 versus donor). C, Representative transmission electron microscopy (TEM) images indicating the endoplasmic reticulum (ER) and mitochondrial contacts in the human hearts of donors and heart failure patients. Asterisks indicate mitochondria; Pound signs indicate ER. Scale bars, 1 μm D, Quantification of the ER adjacent to mitochondria in the heart was normalized by total ER perimeter (mean ± SD, n = 4; **P < 0.01 versus donor). E, Mitochondrial length and width (mean ± SD, n = 4; **P < 0.01 versus donor).