Dynamin-like 120 kDa protein, mitochondrial (OPA1)

Dynamin-like 120 kDa protein, commonly known as OPA1, is a large GTPase localized to the inner mitochondrial membrane where it plays a fundamental role in mitochondrial dynamics [1, 12]. It is essential for the fusion of the inner mitochondrial membrane and the maintenance of cristae architecture, which directly impacts oxidative phosphorylation efficiency and the sequestration of pro-apoptotic factors like cytochrome c [2, 11]. Mutations in the OPA1 gene are the primary cause of Dominant Optic Atrophy (DOA), a condition characterized by the progressive degeneration of retinal ganglion cells and vision loss [3, 6]. Beyond its role in hereditary neuropathies, OPA1 is frequently overexpressed in various cancers, including acute myeloid leukemia and lung cancer, where it promotes tumor cell survival and resistance to apoptosis by stabilizing mitochondrial structure [18, 22]. Therapeutic strategies targeting OPA1 include gene and RNA therapies, such as PYC-001, which aim to restore protein levels in patients with haploinsufficiency-driven optic atrophy [26]. Conversely, small-molecule inhibitors like MYLS22 and Opitor-0 are being developed as anti-cancer agents to disrupt OPA1-mediated cristae stability, thereby sensitizing tumor cells to apoptosis-inducing drugs [18, 23]. Additionally, metabolic therapies like idebenone are used to support mitochondrial function in OPA1-deficient states [31]. Monitoring OPA1 expression and mitochondrial morphology serves as a critical biomarker for assessing disease progression and therapeutic efficacy in both neurodegenerative and oncological contexts [19, 29].

Other names

OPA1Optic atrophy 1MGM1NPGNTGlargeGMitochondrial dynamin-like GTPaseBERHSMTDPS14KIAA0567Optic atrophy protein 1

GTPase inhibition, RNA-mediated expression enhancement, AAV-mediated gene replacement, Metabolic support, Antioxidant activity