OPA1 mutations in dominant optic atrophy: domain-specific defects in mitochondrial fusion and apoptotic regulation.

ABSTRACT:

Background

Autosomal dominant optic atrophy (ADOA), a leading common inherited optic neuropathy, arises from progressive retinal ganglion cell degeneration, often linked to OPA1 mutations. OPA1, a mitochondrial GTPase, regulates mitochondrial fusion, crista structure, and apoptosis. While GTPase-related dysfunction is well-studied, the role of other OPA1 domains in ADOA pathology remains unclear.

Methods

To investigate ADOA-linked OPA1 mutations, we assessed mitochondrial morphology, membrane potential, cytochrome c release, and cell viability in primary cortical neurons and N2a cells expressing OPA1 wild-type or mutant constructs. RNA sequencing and structural predictions (SWISS-MODEL) provided insights into molecular pathways and structural impacts.

Results

Two ADOA

SUBMITTER: Zhang K 

PROVIDER: S-EPMC12020257 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature