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

L. Fülöp, Anikó Rajki, Erika Maka, Mária Judit Molnár, A. Spät

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

The most frequent form of hereditary blindness, autosomal dominant optic atrophy (ADOA), is caused by the mutation of the mitochondrial protein Opa1 and the ensuing degeneration of retinal ganglion cells. Previously we found that knockdown of OPA1 enhanced mitochondrial Ca2+ uptake (Fülöp 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.

Original languageEnglish
Pages (from-to)49-55
Number of pages7
JournalCell Calcium
Volume57
Issue number1
DOIs
Publication statusPublished - 2015

Fingerprint

Autosomal Dominant Optic Atrophy
Mutation
Retinal Ganglion Cells
Mitochondrial Proteins
Blindness
Ganglia
Introns
Genes
Mitochondria
Fibroblasts
Apoptosis

Keywords

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

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology
  • Physiology
  • Medicine(all)

Cite this

Mitochondrial Ca2+ uptake correlates with the severity of the symptoms in autosomal dominant optic atrophy. / Fülöp, L.; Rajki, Anikó; Maka, Erika; Molnár, Mária Judit; Spät, A.

In: Cell Calcium, Vol. 57, No. 1, 2015, p. 49-55.

Research output: Contribution to journalArticle

Fülöp, L. ; Rajki, Anikó ; Maka, Erika ; Molnár, Mária Judit ; Spät, A. / Mitochondrial Ca2+ uptake correlates with the severity of the symptoms in autosomal dominant optic atrophy. In: Cell Calcium. 2015 ; Vol. 57, No. 1. pp. 49-55.
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