Mitochondrial Fission/Fusion and Disease


The mitochondria are a multifaceted organelle, central to the function of all eukaryotic cells. Mitochondria are critical to cell metabolism and critical for regulation of intrinsic cell death pathways. This balance between life and death is reliant on the process of mitochondrial fission and fusion, constantly joining and separating to maintain the mitochondrial network within the cell and to facilitate cellular events such as mitosis, biogenesis and maintenance of mitochondrial integrity via mitophagy. The dynamic fluctuations in the architecture of these organelles is garnering increased attention across a broad range of disciplines and diseases. Such diseases include genetic disorders such as Charcot‐Marie‐Tooth disease type 2A and autosomal‐dominant optic atrophy, as well as pathologies associated with mitochondrial dysfunction such as chronic neurodegeneration such as Parkinson disease, type 2 diabetes and various forms of chronic and acute kidney injury.

Key Concepts

  • Mitochondria undergo constant fission and fusion to maintain function and biogenesis.
  • Impairment of mitochondrial dynamics can result in reduced oxidative phosphorylation and cell death.
  • Impairment of mitochondrial dynamics is associated with diseases involving cells abundant in mitochondria.
  • Mitochondrial fusion is associated with energy production.
  • Mitochondrial fragmentation is associated with mitochondrial dysfunction and turnover by mitophagy.

Keywords: mitochondria; fission; fusion; kidney disease; neurodegeneration; cardiovascular disease; cancer

Figure 1. Mitochondrial fission. (a) Drp1 translocates from cytosol to mitochondria to initiate the fission process; (b) Drp1 interacts with MiD49/51, Mff and/or Fis1 to form a ring around the mitochondria to pinch the organelle in half; (c) Fragmented mitochondria separate.
Figure 2. Mitochondrial fusion. (a) Fragmented mitochondria come together through interaction of Opa1 on the inner mitochondrial membrane and Mfn1/2 on the outer mitochondrial membrane; (b) Once the adjacent mitochondria become tethered, the outer mitochondrial membranes fuse together to form a new elongated mitochondria; (c) Mitochondrial fusion is impaired when long isoforms of Opa1 (L‐Opa1) are cleaved (black arrows) into short isoforms of Opa1 (S‐Opa1) by Oma1 and YME1L in the inner mitochondrial membrane or Romo1, which is stimulated by ROS within the mitochondrial matrix.


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Further Reading

Archer SL (2013) Mitochondrial dynamics – mitochondrial fission and fusion in human diseases. The New England Journal of Medicine 369 (23): 2236–2251.

Chen L, Allison J and Knowlton AA (2014) Mitochondrial dynamics changes in health and genetic diseases. Molecular Biology Reports 41 (11): 7053–7062.

Elgass K, Pakay J, Ryan MT and Palmer CS (2013) Recent advances into the understanding of mitochondrial fission. Biochimica et Biophysica Acta 1833 (3): 150–161.

Higgins GC and Coughlan MT (2014) Mitochondrial dysfunction and mitophagy: the beginning and end to diabetic nephropathy? British Journal of Pharmacology 171 (8): 1917–1942.

Karbowski M and Youle RJ (2011) Regulating mitochondrial outer membrane proteins by ubiquitination and proteasomal degradation. Current Opinion in Cell Biology 23 (4): 476–482.

Richter V, Singh AP, Kvansakul M, Ryan MT and Osellame LD (2015) Splitting up the powerhouse: structural insights into the mechanism of mitochondrial fission. Cellular and Molecular Life Sciences 72 (19): 3695–3707.

Song M and Dorn GW, II (2015) Mitoconfusion: noncanonical functioning of dynamism factors in static mitochondria of the heart. Cell Metabolism 21 (2): 195–205.

Yoon Y, Galloway CA, et al. (2011) Mitochondrial dynamics and diabetes. Antioxidant and Redox Signaling 14 (3): 439–457.

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Higgins, Gavin C, and Coughlan, Melinda T(Jan 2016) Mitochondrial Fission/Fusion and Disease. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0021879]