TY - JOUR
T1 - OPA1-associated disorders: phenotypes and pathophysiology
AU - Amati-Bonneau, Patrizia
AU - Milea, Dan
AU - Bonneau, Dominique
AU - Chevrollier, Arnaud
AU - Ferré, Marc
AU - Guillet, Virginie
AU - Gueguen, Naïg
AU - Loiseau, Dominique
AU - de Crescenzo, Marie-Anne Pou
AU - Verny, Christophe
AU - Procaccio, Vincent
AU - Lenaers, Guy
AU - Reynier, Pascal
AU - Amati-Bonneau, Patrizia
AU - Milea, Dan
AU - Bonneau, Dominique
AU - Chevrollier, Arnaud
AU - Ferré, Marc
AU - Guillet, Virginie
AU - Gueguen, Naïg
AU - Loiseau, Dominique
AU - de Crescenzo, Marie-Anne Pou
AU - Verny, Christophe
AU - Procaccio, Vincent
AU - Lenaers, Guy
AU - Reynier, Pascal
N1 - Keywords: Animals; DNA, Mitochondrial; GTP Phosphohydrolases; Humans; Mitochondrial Diseases; Optic Atrophy, Autosomal Dominant; Optic Nerve; Retinal Ganglion Cells
PY - 2009/10/1
Y1 - 2009/10/1
N2 - The OPA1 gene, encoding a dynamin-like mitochondrial GTPase, is involved in autosomal dominant optic atrophy (ADOA, OMIM #165500). ADOA, also known as Kjer's optic atrophy, affects retinal ganglion cells and the axons forming the optic nerve, leading to progressive visual loss. OPA1 gene sequencing in patients with hereditary optic neuropathies indicates that the clinical spectrum of ADOA is larger than previously thought. Specific OPA1 mutations are responsible for several distinct clinical presentations, such as ADOA with deafness (ADOAD), and severe multi-systemic syndromes, the so-called "ADOA plus" disorders, which involve neurological and neuromuscular symptoms similar to those due to mitochondrial oxidative phosphorylation defects or mitochondrial DNA instability. The study of the various clinical presentations of ADOA in conjunction with the investigation of OPA1 mutations in fibroblasts from patients with optic atrophy provides new insights into the pathophysiological mechanisms of the disease while underscoring the multiple physiological roles played by OPA1 in energetic metabolism, mitochondrial structure and maintenance, and cell death. Finally, OPA1 represents an important new paradigm for emerging neurodegenerative diseases affecting mitochondrial structure, plasticity and functions.
AB - The OPA1 gene, encoding a dynamin-like mitochondrial GTPase, is involved in autosomal dominant optic atrophy (ADOA, OMIM #165500). ADOA, also known as Kjer's optic atrophy, affects retinal ganglion cells and the axons forming the optic nerve, leading to progressive visual loss. OPA1 gene sequencing in patients with hereditary optic neuropathies indicates that the clinical spectrum of ADOA is larger than previously thought. Specific OPA1 mutations are responsible for several distinct clinical presentations, such as ADOA with deafness (ADOAD), and severe multi-systemic syndromes, the so-called "ADOA plus" disorders, which involve neurological and neuromuscular symptoms similar to those due to mitochondrial oxidative phosphorylation defects or mitochondrial DNA instability. The study of the various clinical presentations of ADOA in conjunction with the investigation of OPA1 mutations in fibroblasts from patients with optic atrophy provides new insights into the pathophysiological mechanisms of the disease while underscoring the multiple physiological roles played by OPA1 in energetic metabolism, mitochondrial structure and maintenance, and cell death. Finally, OPA1 represents an important new paradigm for emerging neurodegenerative diseases affecting mitochondrial structure, plasticity and functions.
U2 - 10.1016/j.biocel.2009.04.012
DO - 10.1016/j.biocel.2009.04.012
M3 - Review
C2 - 19389487
SN - 1357-2725
VL - 41
SP - 1855
EP - 1865
JO - International Journal of Biochemistry and Cell Biology
JF - International Journal of Biochemistry and Cell Biology
IS - 10
ER -