线粒体蛋白OPA3通过调节雄性小鼠的钙处理来维持心脏功能
Mitochondrial protein OPA3 sustains cardiac function by regulating calcium handling in male mice.
摘要(中文译文)
心力衰竭（HF）是一种日益加重的全球健康负担，以心肌收缩力受损和进行性重构为特征，其部分驱动因素为钙处理紊乱和线粒体功能障碍。然而，协调这些过程的分子机制仍未被完全阐明。本研究表明，OPA3在人类和小鼠HF中均降低。雄性小鼠心肌细胞特异性敲除Opa3导致进行性扩张型心肌病（DCM），并伴有心肌功能、钙循环和线粒体功能受损。机制上，OPA3形成多聚体，这是其与受磷蛋白（PLN）相互作用所必需的，从而维持肌浆网（SR）钙ATP酶（SERCA2a）活性和钙处理。OPA3定位于线粒体外膜，其缺失损害线粒体功能。心肌细胞特异性过表达Opa3可改善压力超负荷和多柔比星诱导的HF模型中的心脏功能障碍。我们的数据明确了OPA3-PLN-SERCA2a轴在调控线粒体和SR功能中的关键作用，代表了一个潜在的HF治疗靶点。
Abstract
Heart failure (HF) is a growing global health burden characterized by impaired cardiac contractility and progressive remodeling, driven in part by disrupted Ca handling and mitochondrial dysfunction. However, the molecular mechanisms coordinating these processes remain incompletely understood. Here we showed that OPA3 was decreased in both human and murine HF. Cardiomyocyte-specific deletion of Opa3 in male mice led to the progressive dilated cardiomyopathy (DCM), accompanied by impaired myocardial function, calcium cycling and mitochondria function. Mechanistically, OPA3 forms multimers that are required for its interaction with phospholamban (PLN), thereby maintaining sarcoplasmic reticulum (SR) Ca-ATPase (SERCA2a) activity and Ca handling. OPA3 is localized to the mitochondrial outer membrane, and its absence impaired mitochondrial function. Cardiomyocyte-specific overexpression of Opa3 improved cardiac dysfunction in both pressure overload- and doxorubicin-induced HF models. Our data define a critical role of OPA3-PLN-SERCA2a axis that regulates both mitochondria and SR function, representing a potential therapeutic target for HF.
如何引用
AMA
Na Geng, Taiwei Chen, Hao Li, Shan Lu, Yuehong Wang, Ling Gao, et al. Mitochondrial protein OPA3 sustains cardiac function by regulating calcium handling in male mice.. Nature communications. 2026; doi:10.1038/s41467-026-73991-4.
APA
Na Geng, Taiwei Chen, Hao Li, Shan Lu, Yuehong Wang, Ling Gao, et al (2026). Mitochondrial protein OPA3 sustains cardiac function by regulating calcium handling in male mice.. Nature communications. https://doi.org/10.1038/s41467-026-73991-4
GB/T 7714
Na Geng, Taiwei Chen, Hao Li, Shan Lu, Yuehong Wang, Ling Gao, et al. Mitochondrial protein OPA3 sustains cardiac function by regulating calcium handling in male mice.[J]. Nature communications, 2026 doi:10.1038/s41467-026-73991-4.
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