Dynamin-like GTPase OPA1, mitochondrial (OPA1) (OPA1)

Dynamin-like GTPase OPA1, mitochondrial is a critical protein located within the inner mitochondrial membrane (IMM) that governs mitochondrial dynamics and organelle architecture [1, 5, 8]. Its primary function involves mediating the fusion of the IMM and maintaining the integrity of mitochondrial cristae, which are essential for efficient oxidative phosphorylation and ATP synthesis [2, 6, 12]. Furthermore, OPA1 plays a pivotal role in regulating apoptosis by sequestering cytochrome c within the cristae, thereby acting as a molecular gatekeeper against premature cell death [6, 11, 15]. Mutations in the OPA1 gene are the primary cause of autosomal dominant optic atrophy (DOA), a condition leading to progressive retinal ganglion cell loss and blindness, and are also associated with multi-systemic 'OPA1-plus' syndromes [2, 17, 20]. In oncology, OPA1 has emerged as a therapeutic target because its inhibition can disrupt the mitochondrial network and cristae structure in malignant cells, triggering apoptosis and overcoming resistance to chemotherapy [1, 12, 14]. Experimental small-molecule inhibitors such as BTM-3566 are currently being investigated for their potential to treat hematologic and solid tumors by modulating these mitochondrial dynamics [12, 14, 22].

Other names

Optic atrophy protein 1Dynamin-like 120 kDa protein, mitochondrialMGM1NPGNTGOptic atrophy 1largeGBERHSMTDPS14

Inhibition of OPA1 leads to mitochondrial fragmentation, disruption of cristae architecture, and the release of pro-apoptotic factors like cytochrome c to induce cell death in cancer; activation or stabilization of OPA1 promotes mitochondrial fusion and preserves bioenergetics in neurodegenerative contexts.