Mitochondrial Homeostasis Mediates Lipotoxicity in the Failing Myocardium

Figure 1. Ceramide structure and synthesis. (a) Schematic diagram illustrating ceramide structure. (b) Simplified ceramide synthesis pathways with essential enzymes in the respective pathway. (c) Schematic presentation of ceramide synthase structure based on previous findings [93,94,95,96,97,98,99,100,101].

Figure 2. Schematic illustration of lipotoxicity-mediated mitochondrial damage.

Figure 3. Visualization of mitochondrial structure. (a) Impaired and disturbed mitochondrial distribution was stained with MitoTracker (green) and visualized with laser scanning microscopy in doxorubicin-treated HL-1 murine cardiomyocytes. Nucleus was stained with Hoechst (blue). (b) mRNA expression of mitochondrial fusion and fission-related genes. Cardiac cell line HL-1 cells treated with doxorubicin showed decreased MFN1 and MFN2 expression but increased DRP1, Mff, and FIS1 expression. Doxorubicin-dependent induction of ceramide level was attenuated upon treatment with the unspecific CerS inhibitor fumonisin B. The fission-related mRNA expression (DRP1, Mff, FIS1) returned to non-significant levels following fumonisin B treatment. Significance was calculated with t-test. * p < 0.05, ** p < 0.01.

Figure 4. Flowchart presents the process of heart failure development following lipotoxicity.