PT  - JOURNAL ARTICLE
AU  - Tomohiro Kimura
AU  - Atsuko K Kimura
AU  - Mindong Ren
AU  - Vernon Monteiro
AU  - Yang Xu
AU  - Bob Berno
AU  - Michael Schlame
AU  - Richard M Epand
TI  - Plasmalogen loss caused by remodeling deficiency in mitochondria
AID  - 10.26508/lsa.201900348
DP  - 2019 Aug 01
TA  - Life Science Alliance
PG  - e201900348
VI  - 2
IP  - 4
4099  - https://www.life-science-alliance.org/content/2/4/e201900348.short
4100  - https://www.life-science-alliance.org/content/2/4/e201900348.full
SO  - Life Sci. Alliance2019 Aug 01; 2
AB  - 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.