Advances in Cardiolipin Analysis: Applications in Central Nervous System Disorders and Nutrition Interventions

Cardiolipin (CL), a unique dimeric phospholipid predominantly enriched in the inner mitochondrial membrane, is a crucial determinant of mitochondrial structure and function. Its content, fatty acyl composition, and oxidation state are associated with mitochondrial bioenergetics, dynamics, and cellular signaling. Disruptions in CL metabolism are increasingly implicated in the pathogenesis of various central nervous system (CNS) disorders, including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, epilepsy, and traumatic brain injury. This narrative review summarizes recent advances in the analytical techniques employed for CL analysis. The principles and applications of mass spectrometry-based platforms, nuclear magnetic resonance, Fourier-transform infrared spectroscopy, atomic force microscopy-infrared spectroscopy, and fluorescent probes were discussed, with an emphasis on their strengths in revealing the structure, composition, dynamics, and spatial distribution of CL. Furthermore, the evidence of CL abnormalities in various CNS disorders was assessed, often showing decreased CL levels, loss of polyunsaturated species, and increased oxidation associated with mitochondrial dysfunction and neuronal apoptosis. Furthermore, the nutritional interventions for CL modulation were discussed, such as polyunsaturated fatty acids, polyphenols, carotenoids, retinoids, alkaloids, and triterpenoids, which summarize their potential health-beneficial effects in remodeling the CL acyl chain, preventing oxidation, and regulating mitochondrial homeostasis. Overall, this review provided insight into integrating CL analysis and dietary modulation in understanding CL-related pathologies in CNS disorders.