Cardiolipin, Mitochondria, and Neurological Disease. (April 2021)

• Record Type: Journal Article
• Authors: Falabella, Micol; Vernon, Hilary J.; Hanna, Michael G.; Claypool, Steven M.; Pitceathly, Robert D.S.
• Is Part Of: Trends in endocrinology and metabolism. Volume 32:Number 4(2021)
• Page Start: 224
• Page End: 237
• Publication Date: 2021-04
• Subjects: cardiolipin -- lipids -- mitochondria -- mitochondrial disease -- nervous system -- neurodegeneration; Endocrinology -- Periodicals; Metabolism -- Periodicals; Metabolism; 616.4
• DOI: 10.1016/j.tem.2021.01.006
• Languages: English
• ISSNs: 1043-2760

Abstract

Abstract : Over the past decade, it has become clear that lipid homeostasis is central to cellular metabolism. Lipids are particularly abundant in the central nervous system (CNS) where they modulate membrane fluidity, electric signal transduction, and synaptic stabilization. Abnormal lipid profiles reported in Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and traumatic brain injury (TBI), are further support for the importance of lipid metablism in the nervous system. Cardiolipin (CL), a mitochondria-exclusive phospholipid, has recently emerged as a focus of neurodegenerative disease research. Aberrant CL content, structure, and localization are linked to impaired neurogenesis and neuronal dysfunction, contributing to aging and the pathogenesis of several neurodegenerative diseases, such as AD and PD. Furthermore, the highly tissue-specific acyl chain composition of CL confers it significant potential as a biomarker to diagnose and monitor the progression in several neurological diseases. CL also represents a potential target for pharmacological strategies aimed at treating neurodegeneration. Given the equipoise that currently exists between CL metabolism, mitochondrial function, and neurological disease, we review the role of CL in nervous system physiology and monogenic and neurodegenerative disease pathophysiology, in addition to its potential application as a biomarker and pharmacological target. Highlights: The central nervous system is rich in lipids that support membrane fluidity, electric signal transduction, and synaptic stabilization. Cardiolipin (CL) is a mitochondria-exclusive phospholipid essential for mitochondrial morphology, bioenergetics, dynamics, and signaling pathways. Alterations in brain CL are associated with impaired neuronal function and neurodegeneration. The highly tissue-specific acyl chain composition of CL confers it significant potential as a biomarker to diagnose and monitor the progression in several neurological diseases. CL represents a potential target for pharmacological strategies aimed at treating neurodegeneration.