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Scientific Commentary |
OPA1 mutations and mitochondrial DNA damage: keeping the magic circle in shape
Unit of Molecular Neurogenetics, Foundation ‘Istituto Neurologico Carlo Besta’, Via Temolo 4 – 20126 Milano, Italy
Correspondence to: E-mail: zeviani@istituto-besta.it
| The first 150 words of the full text of this article appear below. |
Structural instability of mitochondrial DNA (mtDNA), consisting either of large-scale rearrangements, tissue-specific depletion or both, is a major cause of mitochondrial dysfunction and disease in humans (Zeviani and Di Donato, 2004
). Almost 20 years have elapsed since the discovery that single, large-scale deletions (Holt et al., 1988) across short direct repeats (Mita et al., 1990) occur and become clonally expanded (Mita et al., 1989) in the mtDNA of patients with the sporadic form of Kearns–Sayre syndrome (Zeviani et al., 1988) or its milder variant, progressive external ophthalmoplegia (PEO; Moraes et al., 1989). Shortly thereafter, the accumulation of multiple mtDNA-deleted species was observed in families with recurrent cases of PEO transmitted as an autosomal dominant trait (Zeviani et al., 1989). Mendelian inheritance of mtDNA mutations appeared at first to be a contradiction, since this genome is transmitted in