{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nOPA1 is a mitochondria‐resident, dynamin‐related GTPase that is anchored to the inner membrane and exposed to the intermembrane space, where it plays a central role in mitochondrial inner membrane fusion and the maintenance of cristae structure. Its function has been shown to be critical for preserving mitochondrial network integrity and bioenergetic competence, with studies demonstrating that the loss or down‐regulation of OPA1 leads to mitochondrial fragmentation, cristae disorganization, and the subsequent release of cytochrome c that triggers apoptosis. Moreover, OPA1 exists in multiple isoforms generated by alternative splicing and regulated proteolytic cleavage, with the long and short forms acting in concert to enable efficient mitochondrial fusion."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "14"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its role in membrane fusion, OPA1 is pivotal for the regulation of mitochondrial quality control and apoptosis. Proteolytic processing of OPA1 in response to changes in mitochondrial membrane potential or apoptotic stimuli—mediated by proteases such as the m‐AAA protease, OMA1, or Yme1L—modulates the balance between the fusion‐competent long isoforms and the short forms that can participate in maintaining cristae integrity independently of fusion. Disruption of this proteolytic equilibrium not only accelerates cytochrome c release but also impairs mtDNA replication and distribution, thereby compromising mitochondrial function and sensitizing cells to apoptotic triggers."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "15", "end_ref": "28"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nFurthermore, mutations in the OPA1 gene have been firmly linked to a spectrum of human diseases, most notably autosomal dominant optic atrophy (ADOA) and its syndromic variants that include sensorineural deafness, ataxia, and peripheral neuropathy. Aberrations in OPA1 not only compromise mitochondrial fusion and disrupt cristae architecture but also disturb the stability of mitochondrial DNA and impair oxidative phosphorylation, thereby contributing to neurodegeneration and myopathy. Recent studies have also implicated OPA1 in broader cellular processes such as mitophagy, metabolic adaptation, and even angiogenesis, highlighting its multifaceted role in cellular homeostasis and the pathogenesis of mitochondrial disorders."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "29", "end_ref": "42"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Tin Aung, Louise Ocaka, Neil D Ebenezer, et al. 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