Bradshaw Patrick C, Aldridge Jessa L, Jamerson Leah E, McNeal Canah, Pearson A Catherine, Frasier Chad R
Department of Biomedical Sciences, James H. Quillen College of Medicine, East Tennessee State University, Box 70582, Johnson City, TN, 37614, USA.
Department of Biological Sciences, East Tennessee State University, Johnson City, TN, 37614, USA.
Mol Neurobiol. 2025 Jun;62(6):7022-7040. doi: 10.1007/s12035-024-04630-6. Epub 2024 Nov 19.
Cardiolipin (CL) is an essential phospholipid that supports the functions of mitochondrial membrane transporters and oxidative phosphorylation complexes. Due to the high level of fatty acyl chain unsaturation, CL is prone to peroxidation during aging, neurodegenerative disease, stroke, and traumatic brain or spinal cord injury. Therefore, effective therapies that stabilize and preserve CL levels or enhance healthy CL fatty acyl chain remodeling are needed. In the last few years, great strides have been made in determining the mechanisms through which precursors for CL biosynthesis, such as phosphatidic acid (PA), are transferred from the ER to the outer mitochondrial membrane (OMM) and then to the inner mitochondrial membrane (IMM) where CL biosynthesis takes place. Many neurodegenerative disorders show dysfunctional mitochondrial ER contact sites that may perturb PA transport and CL biosynthesis. However, little is currently known on how neuronal mitochondria regulate the synthesis, remodeling, and degradation of CL. This review will focus on recent developments on the role of CL in neurological disorders. Importantly, due to CL species in the brain being more unsaturated and diverse than in other tissues, this review will also identify areas where more research is needed to determine a complete picture of brain and spinal cord CL function so that effective therapeutics can be developed to restore the rates of CL synthesis and remodeling in neurological disorders.
心磷脂（CL）是一种重要的磷脂，可支持线粒体膜转运蛋白和氧化磷酸化复合物的功能。由于其脂肪酰链的高度不饱和性，CL在衰老、神经退行性疾病、中风以及创伤性脑或脊髓损伤过程中容易发生过氧化。因此，需要有效的治疗方法来稳定和维持CL水平，或增强健康的CL脂肪酰链重塑。在过去几年中，在确定CL生物合成前体（如磷脂酸（PA））从内质网（ER）转移到线粒体外膜（OMM），然后转移到CL生物合成发生的线粒体内膜（IMM）的机制方面取得了巨大进展。许多神经退行性疾病表现出线粒体-内质网接触位点功能失调，这可能会干扰PA转运和CL生物合成。然而，目前对于神经元线粒体如何调节CL的合成、重塑和降解知之甚少。本综述将聚焦于CL在神经疾病中作用的最新进展。重要的是，由于大脑中的CL种类比其他组织中的更不饱和且更多样化，本综述还将确定需要更多研究的领域，以全面了解脑和脊髓CL的功能，从而开发出有效的治疗方法来恢复神经疾病中CL的合成和重塑速率。
