OPA1, a molecular regulator of dilated cardiomyopathy

Abstract

Dilated cardiomyopathy (DCM) is a disease with no specific treatment, poor prognosis and high mortality. During DCM development, there is apoptosis, mitochondrial dynamics imbalance and changes in cristae structure. Optic atrophy 1 (OPA1) appears at high frequency in these three aspects. DCM LMNA (LaminA/C) gene mutation can activate TP53, and the study of P53 shows that P53 affects OPA1 through Bak/Bax and OMA1 (a metalloprotease). OPA1 can be considered the missing link between DCMp53 and DCM apoptosis, mitochondrial dynamics imbalance and changes in cristae structure. OPA1 regulates apoptosis by regulating the release of cytochrome c from the mitochondrial matrix through CJs (crisp linkages, located in the inner mitochondrial membrane) and unbalances mitochondrial fusion and fission by affecting mitochondrial inner membrane (IM) fusion. OPA1 is also associated with the formation and maintenance of mitochondrial cristae. OPA1 is not the root cause of DCM, but it is an essential mediator in P53 mediating the occurrence and development of DCM, so OPA1 also becomes a molecular regulator of DCM. This review discusses the implication of OPA1 for DCM from three aspects: apoptosis, mitochondrial dynamics and ridge structure.

Dihydromyricetin regulates RIPK3-CaMKII to prevent necroptosis in high glucose-stimulated cardiomyocytes

“…Previous studies have identified that DRP1 is the mitochondrial fission core component, which is gathered into circular structure to mediate mitochondrial fission by mitochondrial cleavage alongside mitochondrial tubules [ 36 ]. OPA1 maintains fused mitochondrial network, and drives inner membrane fusion at the mitochondrial inner membrane [ 37 ]. These findings revealed that high glucose reduced membrane potential of mitochondria, suppressed ATP production, enhanced DRP1 but decreased OPA1 expression and up-regulated intracellular ROS levels.…”

Pectolinarigenin Improves Oxidative Stress and Apoptosis in Mouse NSC-34 Motor Neuron Cell Lines Induced by C9-ALS-Associated Proline–Arginine Dipeptide Repeat Proteins by Enhancing Mitochondrial Fusion Mediated via the SIRT3/OPA1 Axis

“…OPA1 is a mitochondrial guanosine triphosphatase (GTPase) that is widely distributed in the inner membrane of mitochondrial cristae. Its physiological and functional roles include regulating mitochondrial fusion, controlling mitochondrial cristae structure, maintaining mitochondrial integrity, and inhibiting apoptosis-related cytochrome c release [24]. Mitochondrial disruption, respiratory complex I inactivation, and reduced ATP production have been observed in neural cells derived from OPA1mutated induced pluripotent stem cells [25].…”