OPA 1 and Its Clinical Implications

Abstract 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.