Cardiolipin Regulates Mitochondrial Ultrastructure and Function in Mammalian Cells

Abstract

Cardiolipin (CL) is a unique, tetra-acylated diphosphatidylglycerol lipid that mainly localizes in the inner mitochondria membrane (IMM) in mammalian cells and plays a central role in regulating mitochondrial architecture and functioning. A deficiency of CL biosynthesis and remodeling perturbs mitochondrial functioning and ultrastructure. Clinical and experimental studies on human patients and animal models have also provided compelling evidence that an abnormal CL content, acyl chain composition, localization, and level of oxidation may be directly linked to multiple diseases, including cardiomyopathy, neuronal dysfunction, immune cell defects, and metabolic disorders. The central role of CL in regulating the pathogenesis and progression of these diseases has attracted increasing attention in recent years. In this review, we focus on the advances in our understanding of the physiological roles of CL biosynthesis and remodeling from human patients and mouse models, and we provide an overview of the potential mechanism by which CL regulates the mitochondrial architecture and functioning.

Quantitative Lipid Profiling Reveals Major Differences between Liver Organoids with Normal Pi*M and Deficient Pi*Z Variants of Alpha-1-antitrypsin

“…The DEG analysis revealed a significant number of mitochondrial genes of oxidative phosphorylation to be overexpressed in ZZ-ORG. As already mentioned, cardiolipins specifically were found to be higher expressed in ZZ-ORG than in MM-ORG [31].…”

“…This structural alteration in lipid rafts has been related to impaired liver function [30]. Finally, cardiolipins, which are also higher in ZZ-ORG, are among the most abundant lipids in the inner mitochondrial membrane, playing roles in mitochondria stability, metabolism, and dynamics [31]. It is conceivable that abnormalities in the content and/or the composition of cardiolipins may negatively impact mitochondrial function, with implications in diseases such as NAFLD [32].…”

Mitochondrial Bioenergetics, Redox Balance, and Calcium Homeostasis Dysfunction with Defective Ultrastructure and Quality Control in the Hippocampus of Aged Female C57BL/6J Mice

“…Increased density of cristae shows a higher electron density and may allow for a major amount of ETC complexes and, consequently, higher ATP production via aerobic respiration [ 67 , 68 ]. Thus, the reduction in electrodensity of mitochondria that our results shows could be related to a reduction in cristae number, which implies less ETC density, and also a reduction in the formation of supercomplexes in the IMM, which is correlated with mitochondrial bioenergetic dysfunction [ 69 , 70 , 71 ]. During aging, there is a reduction in both cristae density and supercomplex formation in liver mitochondria; however, there are no changes to heart mitochondria [ 70 ], suggesting that these alterations are organ-specific.…”

Acid Sphingomyelinase Deficiency Type B Patient-Derived Liver Organoids Reveals Altered Lysosomal Gene Expression and Lipid Homeostasis

“…Defects in cardiolipin content could have implications for the regulation of mitochondrial function. Alterations in cardiolipins have been linked to the pathogenesis and progression of various metabolic diseases, cardiomyopathies, Barth’s syndrome, and Parkinson’s disease [ 56 , 57 ].…”