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Review
. 2021 Feb 2;22(3):1498.
doi: 10.3390/ijms22031498.

Mitochondrial Homeostasis Mediates Lipotoxicity in the Failing Myocardium

Tom Kretzschmar  1 , Jasmine M F Wu  1 , P Christian Schulze  1
Affiliations
Review

Mitochondrial Homeostasis Mediates Lipotoxicity in the Failing Myocardium

Tom Kretzschmar et al. Int J Mol Sci. .

Abstract

Heart failure remains the most common cause of death in the industrialized world. In spite of new therapeutic interventions that are constantly being developed, it is still not possible to completely protect against heart failure development and progression. This shows how much more research is necessary to understand the underlying mechanisms of this process. In this review, we give a detailed overview of the contribution of impaired mitochondrial dynamics and energy homeostasis during heart failure progression. In particular, we focus on the regulation of fatty acid metabolism and the effects of fatty acid accumulation on mitochondrial structural and functional homeostasis.

Keywords: heart failure; lipotoxicity; metabolism; mitochondrial homeostasis.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
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
Figure 2
Schematic illustration of lipotoxicity-mediated mitochondrial damage.
Figure 3
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
Figure 4
Flowchart presents the process of heart failure development following lipotoxicity.
See this image and copyright information in PMC

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