Abstract
Lipid homeostasis is crucial in human health. Barth syndrome (BTHS), a life-threatening disease typically diagnosed with cardiomyopathy and neutropenia, is caused by mutations in the mitochondrial transacylase tafazzin. By high-resolution 31P nuclear magnetic resonance (NMR) with cryoprobe technology, recently we found a dramatic loss of choline plasmalogen in the tafazzin-knockdown (TAZ-KD) mouse heart, besides observing characteristic cardiolipin (CL) alterations in BTHS. In inner mitochondrial membrane where tafazzin locates, CL and diacyl phosphatidylethanolamine are known to be essential via lipid-protein interactions reflecting their cone shape for integrity of respiratory chain supercomplexes and cristae ultrastructure. Here, we investigate the TAZ-KD brain, liver, kidney, and lymphoblast from patients compared with controls. We identified common yet markedly cell type-dependent losses of ethanolamine plasmalogen as the dominant plasmalogen class therein. Tafazzin function thus critically relates to homeostasis of plasmalogen, which in the ethanolamine class has conceivably analogous and more potent molecular functions in mitochondria than diacyl phosphatidylethanolamine. The present discussion of a loss of plasmalogen-protein interaction applies to other diseases with mitochondrial plasmalogen loss and aberrant forms of this organelle, including Alzheimer's disease.
Highlights
Lipid composition of the cell varies depending on the type of cell, tissue, organ, or organism for their respective biological requirements associated with the structural and functional integrity of the cell membranes (Kimura et al, 2016; Harayama & Riezman, 2018)
Barth syndrome (BTHS) has initially been recognized with its marked symptoms of cardioskeletal myopathy and neutropenia, increasing knowledge and understanding are being gained, indicating that this disease is characterized by a broad range of clinical symptoms (Clarke et al, 2013)
High-resolution 31P nuclear magnetic resonance (NMR) experiments on the brain, liver, and kidney of the TAZ-KD mice and lymphoblast cells derived from BTHS patients
Summary
Lipid composition of the cell varies depending on the type of cell, tissue, organ, or organism for their respective biological requirements associated with the structural and functional integrity of the cell membranes (Kimura et al, 2016; Harayama & Riezman, 2018). Tafazzin critically controls lipid species in different types of cells in the human body, regulating diverse physiological functions (Kimura et al, 2016). Deficiency in tafazzin function is known to cause prominent alterations related to the state of cardiolipin (CL) in mitochondria: a decrease in the level, accumulation of monolysocardiolipin (MLCL), and diversification of acyl species in contrast to the normal control, for example, with a dominant CL species of tetralinoleoyl (18:2) in the heart, liver, and kidney (Vreken et al, 2000; Schlame et al, 2002, 2005; Gu et al, 2004). The normal CL level, which is made of a cell type–specific acyl species distribution, is important in structural and functional regulation of the individual respiratory complexes and their supercomplexes, as well as maintenance of the cristae ultrastructure (Sesaki et al, 2006; Osman et al, 2009; Mileykovskaya & Dowhan, 2014; Dudek & Maack, 2017; Musatov & Sedlak, 2017)
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