A novel deletion in the GTPase domain of OPA1 causes defects in mitochondrial morphology and distribution, but not in function

摘要: Autosomal dominant optic atrophy (ADOA), the commonest cause of inherited atrophy, is caused by mutations in ubiquitously expressed gene 1 (OPA1), involved fusion and biogenesis inner membrane mitochondria. Bioenergetic failure, mitochondrial network abnormalities increased apoptosis have all been proposed as possible causal factors. However, their relative contribution to pathogenesis well prominent susceptibility retinal ganglion cell (RGC) this disease remains uncertain. Here we identify a novel deletion OPA1 GTPase domain three patients affected ADOA. Muscle biopsy showed neurogenic abnormal morphology distribution Confocal microscopy revealed fragmentation fibroblasts myotubes, where mitochondria were also unevenly distributed, with clustered organelles alternating areas sparse. These not associated altered bioenergetics or pro-apoptotic stimuli. Therefore, changes shape can be independent other reported effects mutations, therefore may primary disease. The arrangement RGCs, which degenerate ADOA, exquisitely sensitive disturbance, lead bioenergetic crisis and/or induction apoptosis. Our results highlight importance dynamics per se, point loss fine positioning axons RGCs explanation for predominant degeneration