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Mitochondrial Dynamics in Health and Disease

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Mitochondria and Their Role in Cardiovascular Disease

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Abstract

The two opposing highly regulated processes, division (fission) and fusion, determine cell-type-specific mitochondrial morphology, intracellular distribution, and activity. These finely tuned processes modulate a variety of mitochondrial functions allowing living cells to respond properly to frequently changing environmental conditions. Tightly controlled balance between fusion and fission is of particular importance in the high-energy-demanding cells, such as cardiac, skeletal muscle, or neuronal cells. A shift toward fission leads to mitochondrial fragmentation, observed in quiescent cells, while a shift toward fusion results in the formation of the large mitochondrial networks, found in metabolically active cells.

Large dynamin-related proteins, mitofusins (MFN1, MFN2) and optic atrophy 1 (OPA1) protein, constitute the core machinery promoting mitochondrial fusion. MFN1 and MFN2 are localized on the mitochondrial outer membrane (MOM) and mediate MOM fusion, while OPA1, located in the mitochondrial inner membrane (MIM), promotes fusion of the MIM as well as cristae remodeling. A dynamin-related protein 1 (DRP1), fission 1 (FIS1) protein, and mitochondrial fission factor (MFF) are core components of mitochondrial fission machinery in human cells. All three fission proteins are localized in the MOM, while currently very little is known about fission of the MIM.

Impairment of mitochondrial dynamics has been associated with various human disorders. Currently the most characterized mutations in components involved in mitochondrial dynamics have been found in inherited neurodegenerative disorders, such as autosomal dominant optic atrophy, Charcot-Marie-Tooth neuropathy, abnormal brain development, and the Wolf-Hirschhorn syndrome. Defects in mitochondrial dynamics also contribute to the pathogenesis of age-related progressive neurodegenerative disorders, such as Alzheimer’s, Parkinson’s, and Huntington’s diseases.

Although the myocardium is characterized by high levels of the major factors involved in mitochondrial fusion and fission, the role of mitochondrial dynamics in the heart has only begun to be uncovered. Emerging evidence strongly suggests that impairment of balance of mitochondrial fusion and fission can be associated with various cardiovascular diseases, including ischemia-reperfusion injury (IRI), various cardiomyopathies, and heart failure (HF).

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  1. The Molecular Cardiology and Neuromuscular Institute, Highland Park, NJ, USA

    José Marín-García M.D.

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Marín-García, J. (2013). Mitochondrial Dynamics in Health and Disease. In: Mitochondria and Their Role in Cardiovascular Disease. Springer, Boston, MA. https://doi.org/10.1007/978-1-4614-4599-9_17

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