Dysregulated mitophagy and mitochondrial organization in optic atrophy due to OPA1 mutations.

ABSTRACT:

Objective

To investigate mitophagy in 5 patients with severe dominantly inherited optic atrophy (DOA), caused by depletion of OPA1 (a protein that is essential for mitochondrial fusion), compared with healthy controls.

Methods

Patients with severe DOA (DOA plus) had peripheral neuropathy, cognitive regression, and epilepsy in addition to loss of vision. We quantified mitophagy in dermal fibroblasts, using 2 high throughput imaging systems, by visualizing colocalization of mitochondrial fragments with engulfing autophagosomes.

Results

Fibroblasts from 3 biallelic OPA1(-/-) patients with severe DOA had increased mitochondrial fragmentation and mitochondrial DNA (mtDNA)-depleted cells due to decreased levels of OPA1 protein. Similarly, in siRNA-treated control fibroblast

SUBMITTER: Liao C 

PROVIDER: S-EPMC5224718 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature