Cardiolipin Remodeling in Cardiovascular Diseases: Implication for Mitochondrial Dysfunction

IF 5.6 2区医学 Q1 PHYSIOLOGY

Acta Physiologica Pub Date : 2025-06-18 DOI:10.1111/apha.70073

Huijie Zhang, Fengzhi Yu, Zhenjun Tian, Dandan Jia

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引用次数: 0

Abstract

Aim

Mitochondrial dysfunction is pivotal in both the development and progression of cardiovascular diseases (CVDs), though its exact mechanisms remain unclear. Cardiolipin (CL), a key mitochondrial phospholipid, is involved in various mitochondrial functions, including dynamics, membrane integrity, oxidative phosphorylation, mitochondrial DNA maintenance, and mitophagy. Due to enzyme limitations in the CL biosynthesis pathway, premature CL undergoes remodeling to acquire the proper acyl content for its function. Disruption in CL composition leads to mitochondrial dysfunction, contributing significantly to CVDs. The purpose of this review is to explore the role of CL remodeling in the mechanism of mitochondrial dysfunction that occurs in CVDs.

Methods

This review examines CL’s critical role in mitochondrial function, the consequences of CL deficiencies in CVDs, and the impact of mutations or deficiencies in CL remodeling enzymes-tafazzin (TAZ), Acyl-CoA:lysocardiolipin acyltransferase-1 (ALCAT1), and Monolysocardiolipin acyltransferase (MLCLAT1)-on CL homeostasis, mitochondrial function, and CVDs pathogenesis. Emerging CL-targeted therapies are also reviewed.

Results

Proper CL function is crucial for mitochondrial health and cardioprotection. Pathological CL remodeling due to mutations or deficiencies in TAZ, ALCAT1, or MLCLAT1, drives mitochondrial dysfunction and accelerates CVDs progression. Based on these insights, current CL-based therapeutic strategies are also summarized, including precision medicine/gene therapy, targeted pharmacotherapy, and dietary interventions.

Conclusion

Targeting CL may represent a promising clinical therapeutic strategy for CVDs.

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心血管疾病中的心磷脂重塑：对线粒体功能障碍的影响

目的线粒体功能障碍在心血管疾病（cvd）的发生和发展中起着关键作用，但其确切机制尚不清楚。心磷脂（Cardiolipin， CL）是一种关键的线粒体磷脂，参与线粒体的各种功能，包括动力学、膜完整性、氧化磷酸化、线粒体DNA维持和线粒体自噬。由于CL生物合成途径中的酶限制，过早的CL经历重塑以获得适当的酰基含量以发挥其功能。CL组成的破坏导致线粒体功能障碍，显著促进心血管疾病。这篇综述的目的是探讨线粒体功能障碍发生在心血管疾病的机制中CL重塑的作用。方法本文综述了CL在线粒体功能中的关键作用，cvd中CL缺乏的后果，以及CL重塑酶——他法津（TAZ）、酰基辅酶a：溶心磷脂酰基转移酶1 （ALCAT1）和单聚心磷脂酰基转移酶（MLCLAT1）的突变或缺乏对CL稳态、线粒体功能和cvd发病机制的影响。新兴的cl靶向治疗也进行了回顾。结果适当的CL功能对线粒体健康和心脏保护至关重要。由于TAZ、ALCAT1或MLCLAT1的突变或缺陷导致的病理性CL重塑驱动线粒体功能障碍并加速cvd的进展。基于这些见解，总结了目前基于cl的治疗策略，包括精准医学/基因治疗、靶向药物治疗和饮食干预。结论靶向CL可能是一种很有前途的cvd临床治疗策略。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Acta Physiologica 医学-生理学

CiteScore

11.80

自引率

15.90%

发文量

182

审稿时长

4-8 weeks

期刊介绍： Acta Physiologica is an important forum for the publication of high quality original research in physiology and related areas by authors from all over the world. Acta Physiologica is a leading journal in human/translational physiology while promoting all aspects of the science of physiology. The journal publishes full length original articles on important new observations as well as reviews and commentaries.