患者来源的诱导多能干细胞模型揭示了异常线粒体动力学和心肌病之间的机制联系。

IF 3.1 3区医学 Q1 PEDIATRICS

Pediatric Research Pub Date : 2025-07-09 DOI:10.1038/s41390-025-04278-5

Chrishan J Ramachandra

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引用次数: 0

摘要

影响：DNM1L突变损害线粒体裂变，导致心肌细胞能量不足和收缩功能障碍，并揭示了DNM1L在神经系统疾病之外的心脏作用。来自DNM1L突变患者的ipsc心肌细胞表现出线粒体缺陷和心肌病表型，为解剖疾病机制和确定个性化治疗提供了一个强大的模型。线粒体动力学破坏直接导致钙处理不当和收缩功能障碍，将裂变/融合途径定位为心肌病治疗中有希望的治疗靶点。

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Patient-derived induced pluripotent stem cell models reveal mechanistic links between aberrant mitochondrial dynamics and cardiomyopathy.

Impact: DNM1L mutations impair mitochondrial fission, leading to cardiomyocyte energy deficits and contractile dysfunction, and reveal a cardiac role for DNM1L beyond neurological disease. iPSC-cardiomyocytes derived from patients with DNM1L mutations demonstrate mitochondrial defects and cardiomyopathy phenotypes, offering a robust model to dissect disease mechanisms and identify personalised therapies. Disrupted mitochondrial dynamics directly lead to calcium mishandling and contractile dysfunction, positioning fission/fusion pathways as promising therapeutic targets in cardiomyopathy treatment.

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来源期刊

Pediatric Research 医学-小儿科

CiteScore

6.80

自引率

5.60%

发文量

473

审稿时长

3-8 weeks

期刊介绍： Pediatric Research publishes original papers, invited reviews, and commentaries on the etiologies of children''s diseases and disorders of development, extending from molecular biology to epidemiology. Use of model organisms and in vitro techniques relevant to developmental biology and medicine are acceptable, as are translational human studies