Shi Yuguang
Department of Cellular and Molecular Physiology, Pennsylvania State University College of Medicine, Hershey, PA 17033, U.S.A.
J Biomed Res. 2010 Jan;24(1):6-15. doi: 10.1016/S1674-8301(10)60003-6.
Cardiolipin (CL) is a phospholipid exclusively localized in inner mitochondrial membrane where it is required for oxidative phosphorylation, ATP synthesis, and mitochondrial bioenergetics. The biological functions of CL are thought to depend on its acyl chain composition which is dominated by linoleic acids in metabolically active tissues. This unique feature is not derived from the de novo biosynthesis of CL, rather from a remodeling process that involves in phospholipases and transacylase/acyltransferase. The remodeling process is also believed to be responsible for generation of CL species that causes oxidative stress and mitochondrial dysfunction. CL is highly sensitive to oxidative damages by reactive oxygen species (ROS) due to its high content in polyunsaturated fatty acids and location near the site of ROS production. Consequently, pathological remodeling of CL has been implicated in the etiology of mitochondrial dysfunction commonly associated with diabetes, obesity, heart failure, neurodegeneration, and aging that are characterized by oxidative stress, CL deficiency, and abnormal CL species. This review summarizes recent progresses in molecular, enzymatic, lipidomic, and metabolic studies that support a critical regulatory role of pathological CL remodeling as a missing link between oxidative stress and mitochondrial dysfunction in metabolic diseases and aging.
心磷脂（CL）是一种仅存在于线粒体内膜的磷脂，在氧化磷酸化、ATP合成和线粒体生物能量学过程中发挥着重要作用。CL的生物学功能被认为取决于其酰基链组成，在代谢活跃的组织中，亚油酸占主导地位。这一独特特性并非源于CL的从头生物合成，而是源于一个涉及磷脂酶和转酰基酶/酰基转移酶的重塑过程。人们还认为，重塑过程会导致产生引起氧化应激和线粒体功能障碍的CL种类。由于CL富含多不饱和脂肪酸且位于活性氧产生部位附近，因此它对活性氧（ROS）引起的氧化损伤高度敏感。因此，CL的病理性重塑被认为与糖尿病、肥胖、心力衰竭、神经退行性变和衰老等常见的线粒体功能障碍病因有关，这些疾病的特征是氧化应激、CL缺乏和CL种类异常。这篇综述总结了分子、酶学、脂质组学和代谢研究方面的最新进展，这些研究支持病理性CL重塑作为代谢性疾病和衰老中氧化应激与线粒体功能障碍之间缺失环节的关键调节作用。
