Mitochondrial optic neuropathies: how two genomes may kill the same cell type?
Ocular involvement is a prevalent feature in mitochondrial diseases. Leber's hereditary optic neuropathy (LHON) and dominant optic atrophy (DOA) are both non-syndromic optic neuropathies with a mitochondrial etiology. LHON is associated with point mutations in the mitochondrial DNA (mtDNA), which affect subunit genes of complex I. The majority of DOA patients harbor mutations in the nuclear-encoded protein OPA1, which is targeted to mitochondria and participates to cristae organization and mitochondrial network dynamics. In both disorders the retinal ganglion cells (RGCs) are specific cellular targets of the degenerative process. We here review the clinical features and the genetic bases, and delineate the possible common pathomechanism for both these disorders.
Carelli
Valerio
V
Laboratory of Neurogenetics, Department of Neurological Sciences, University of Bologna, Via Ugo Foscolo 7, Bologna, 40123, Italy. valerio.carelli@unibo.it
La Morgia
Chiara
C
Iommarini
Luisa
L
Carroccia
Rosanna
R
Mattiazzi
Marina
M
Sangiorgi
Simonetta
S
Farne'
Sabrina
S
Maresca
Alessandra
A
Foscarini
Beatrice
B
Lanzi
Lucia
L
Amadori
Marcello
M
Bellan
Marzio
M
Valentino
Maria Lucia
ML
D017209:Apoptosis / Q000235:genetics / Q000502:physiology; D004272:DNA, Mitochondrial / Q000235:genetics; D042967:Electron Transport Complex I / Q000235:genetics / Q000378:metabolism; D006801:Humans; D028361:Mitochondrial Diseases / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D008954:Models, Biological; D009154:Mutation; D029241:Optic Atrophy, Autosomal Dominant / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D029242:Optic Atrophy, Hereditary, Leber / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D009901:Optic Nerve Diseases / Q000235:genetics / Q000378:metabolism / Q000473:pathology*
D004272:DNA, Mitochondrial; D042967:Electron Transport Complex I