RT Journal Article
SR Electronic
T1 Plasmalogen loss caused by remodeling deficiency in mitochondria
JF Life Science Alliance
JO Life Sci. Alliance
FD Life Science Alliance LLC
SP e201900348
DO 10.26508/lsa.201900348
VO 2
IS 4
A1 Tomohiro Kimura
A1 Atsuko K Kimura
A1 Mindong Ren
A1 Vernon Monteiro
A1 Yang Xu
A1 Bob Berno
A1 Michael Schlame
A1 Richard M Epand
YR 2019
UL https://www.life-science-alliance.org/content/2/4/e201900348.abstract
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.