OPA1 and Its Clinical Implications


Autosomal dominant optic atrophy (ADOA) or Kjer disease (MIM #165500) is a primary inherited nonsyndromic optic neuropathy that results in loss of retinal ganglion cells, leading to the clinical appearance of optic atrophy. It is caused by mutations in optic atrophy 1 (OPA1), a dynamin‐related protein of the inner mitochondrial membrane. Recent evidence supports a role for OPA1 in the regulation of the process of cristae remodelling during apoptosis, by which the complete release of mitochondrial stores of cytochrome c is achieved, supporting a role for apoptosis in the pathogenesis of ADOA. Here we review the basic clinical features of ADOA, the biology of OPA1 and its role in the regulation of mitochondrial shape changes during apoptosis.

Key concepts

  • Mitochondrial shape changes during apoptosis.

  • Cristae are the main store of cytochrome c.

  • The complete release of cytochrome c is accompanied by the remodelling of the cristae.

  • The dynamin‐related protein OPA1 regulates the shape of the cristae.

  • Dis‐oligomerization of OPA1 is a key event in the release of cytochrome c during apoptosis.

Keywords: mitochondria; apoptosis; fusion; fission; cristae remodelling; cytochrome c release

Figure 1.

A cartoon depicting the OPA1‐containing oligomer at the cristae junction. The cristae is represented as the fold of the (IMM). The soluble and membrane bound OPA1 forms interact to form an oligomer. The specified Flag and His tag refer to the (Frezza et al., ) paper in which tagged forms were employed to verify the composition of the OPA1 oligomer.



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Further Reading

Amati‐Bonneau P, Valentino ML, Reynier P et al. (2008) OPA1 mutations induce mitochondrial DNA instability and optic atrophy ‘plus’ phenotypes. Brain 131: 338–351.

Cereghetti GM and Scorrano L (2006) The many shapes of mitochondrial death. Oncogene 25: 4717–4724.

Scorrano L and Korsmeyer SJ (2003) Mechanisms of cytochrome c release by proapoptotic BCL‐2 family members. Biochemical and Biophysical Research Communications 304: 437–444.

Spinazzi M, Cazzola S, Bortolozzi M et al. (2008) A novel deletion in the GTPase domain of OPA1 causes defects in mitochondrial morphology and distribution, but not in function. Human Molecular Genetics 17: 3291–3302.

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Trevisson, Eva, Salviati, Leonardo, and Scorrano, Luca(Dec 2009) OPA1 and Its Clinical Implications. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0021785]