Mitochondrial dynamics in heart failure

Abstract

Mitochondria have been widely studied for their critical role in cellular metabolism, energy production, and cell death. New developments in research on mitochondria derived from studies in yeast have led to the discovery of entirely new mitochondrial processes that have implications for mitochondrial function in heart failure. Recent studies have identified that maintaining normal mitochondrial morphology and function depends on the dynamic balance of mitochondrial fusion and fission (division). Mitochondrial fusion and fission are constant ongoing processes, which are essential for the maintenance of normal mitochondrial function. Studies in heart failure have been limited but suggest a possible reduction in mitochondrial fusion. As mitochondrial fusion and fission have important links to apoptosis, a key mechanism of loss of cardiac myocytes in heart failure, there are many implications for both heart failure research and treatment.

Figure 1

Diagram summarizes mitochondrial fusion and fission. Mfn1 and Mfn2 contribute to mitochondrial outer membrane (MOM) fusion and OPA1 is involved in the mitochondrial inner membrane (MIM) fusion. The complete fusion of two mitochondria needs both of these MOM and MIM events. On the other hand, Fis1 and Drp1 divide one mitochondria into two. When fission exceeds fusion, small fragmented mitochondria predominate.

Figure 2

Representative EM images for mitochondria from Sham and HF rat left ventricles. In sham control myocytes, mitochondria are well organized and compacted between contractile filaments or adjacent to the sarcolemma. However, in heart failure mitochondria are disorganized and smaller compared to sham, suggesting increased mitochondrial fission vs. fusion in HF. Bar = 500nm, M = mitochondria.