Mitochondrial Ca2+ uptake correlates with the severity of the symptoms in autosomal dominant optic atrophy

作者：Fueloep Laszlo; Rajki Aniko; Maka Erika; Molnar Maria Judit; Spaet Andras

来源：Cell Calcium, 2015, 57(1): 49-55.

DOI：10.1016/j.ceca.2014.11.008

• Optic atrophy
• Fibroblast
• OPA1
• Calcium ion
• Mitochondria
• Apoptosis
• Ganglion cell

The most frequent form of hereditary blindness, autosomal dominant optic atrophy (ADOA), is caused by the mutation of the mitochondrial protein Opal and the ensuing degeneration of retinal ganglion cells. Previously we found that knockdown of OPA1 enhanced mitochondrial Ca2+ uptake (Fulop et al., 2011). Therefore we studied mitochondrial Ca2+ metabolism in fibroblasts obtained from members of an ADOA family. Gene sequencing revealed heterozygosity for a splice site mutation (c. 984+1G>A) in intron 9 of the OPA1 gene. ADOA cells showed a higher rate of apoptosis than control cells and their mitochondria displayed increased fragmentation when forced to oxidative metabolism. The ophthalmological parameters critical fusion frequency and ganglion cell-inner plexiform layer thickness were inversely correlated to the evoked mitochondrial Ca2+ signals. The present data indicate that enhanced mitochondrial Ca2+ uptake is a pathogenetic factor in the progress of ADOA.

• 出版日期2015-1