Zhang Huijie, Yu Fengzhi, Tian Zhenjun, Jia Dandan
School of Exercise and Health, Shanghai University of Sport, Shanghai, China.
Institute of Sports and Exercise Biology, Shaanxi Normal University, Xi'an, China.
Acta Physiol (Oxf). 2025 Jul;241(7):e70073. doi: 10.1111/apha.70073.
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.
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.
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.
Targeting CL may represent a promising clinical therapeutic strategy for CVDs.
线粒体功能障碍在心血管疾病（CVD）的发生和发展中起关键作用，但其确切机制仍不清楚。心磷脂（CL）是一种关键的线粒体磷脂，参与多种线粒体功能，包括动态变化、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存在局限性，过早形成的CL会进行重塑以获得具有适当酰基含量的功能形式。CL组成的破坏会导致线粒体功能障碍，这在很大程度上促成了CVD。本综述的目的是探讨CL重塑在CVD中发生的线粒体功能障碍机制中的作用。
本综述研究了CL在线粒体功能中的关键作用、CL缺乏在CVD中的后果，以及CL重塑酶——tafazzin（TAZ）、酰基辅酶A：溶血心磷脂酰基转移酶-1（ALCAT1）和单溶血心磷脂酰基转移酶（MLCLAT1）的突变或缺乏对CL稳态、线粒体功能和CVD发病机制产生的影响。还对新兴的以CL为靶点的治疗方法进行了综述。
适当的CL功能对于线粒体健康和心脏保护至关重要。由于TAZ、ALCAT1或MLCLAT1的突变或缺乏导致的病理性CL重塑会引发线粒体功能障碍并加速CVD的进展。基于这些见解，还总结了当前基于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。
以CL为靶点可能是一种有前景的CVD临床治疗策略。
