Fig. 4.

Activation of UPR^mtpartly reduces sepsis-induced myocardial injury and mitochondrial dysfunction in FUNDC1-knockout mice. FUNDC1^f/f and cardiomyocyte-specific FUNDC1 knockout (FUNDC1^CKO) mice were injected intraperitoneally with a single dose of PBS or LPS (5 mg/kg) to induce septic cardiomyopathy. Blood and heart samples were isolated 48 h after LPS injection. To induce UPR^mtin vivo, mice were injected with oligomycin (500 μg/kg) intraperitoneally in sterile saline with 0.1% DMSO. A-C. Echocardiographic data showing left ventricular ejection fraction (LVEF), left ventricular diastolic dimension (LVDd), and fractional shortening (FS) in FUNDC1^CKO and FUNDC1^f/f mice in the presence of LPS or oligomycin. D-F. ELISA analysis of the concentration of cardiac injury markers, including LDH, troponin T, and CK-MB. G-H. The AC16 human ventricular cardiomyocyte cell line was treated with 10 μg/mL of LPS to induce sepsis-related cardiomyocyte damage. siRNA against FUNDC1 (si-FUNDC1) was transfected into AC15 to inhibit mitophagy activation. Oligomycin, an inducer of UPR^mt, was used to culture AC16 cells. Next, cells were stained with JC-1 to observe changes in the mitochondrial membrane potential. I-J. AC16 cells were stained with the MitoSOX red mitochondrial superoxide indicator to show changes in mitochondrial ROS. K-L. Mitophagy activity was observed using the mt-Keima assay. A yellow signal highlights increased mitophagic flux within cardiomyocytes. Data are presented as mean ± SEM, normalized per 1000 cardiomyocytes. n = 6 per group. *P<0.05. (For interpretation of the references to colour in this figure legend, the reader is referred to the Web version of this article.)