Interplay between cardiolipin and plasmalogens in Barth syndrome

J Inherit Metab Dis. 2021 Oct 16. doi: 10.1002/jimd.12449. Online ahead of print.


Barth syndrome (BTHS) is a rare inherited metabolic disease resulting from mutations in the gene of the enzyme tafazzin, which catalyzes the acyl chain remodeling of the mitochondrial-specific lipid cardiolipin (CL). Tissue samples of individuals with BTHS present abnormalities in the level and the molecular species of CL. In addition, in tissues of a tafazzin knockdown mouse as well as in cells derived from BTHS patients it has been shown that plasmalogens, a subclass of glycerophospholipids, also have abnormal levels. Likewise, administration of a plasmalogen precursor to cells derived from BTHS patients led to an increase in plasmalogen and to some extent CL levels. These results indicate an interplay between CL and plasmalogens in BTHS. This interdependence is supported by the concomitant loss in these lipids in different pathological conditions. However, currently the molecular mechanism linking CL and plasmalogens is not fully understood. Here, a review of the evidence showing the linkage between the levels of CL and plasmalogens is presented. In addition, putative mechanisms that might play a role in this interplay are proposed. Finally, the opportunity of therapeutic approaches based on the regulation of plasmalogens as new therapies for the treatment of BTHS is discussed.

Keywords: Barth syndrome; cardiolipin; lipid disorders; lipid metabolism; plasmalogen replacement therapy; plasmalogens.

Publication types

  • Review