Open AccessCardiac‐specific succinate dehydrogenase deficiency in Barth syndrome
Author(s) -
Dudek Jan,
Cheng IFen,
Chowdhury Arpita,
Wozny Katharina,
Balleininger Martina,
Reinhold Robert,
Grunau Silke,
Callegari Sylvie,
Toischer Karl,
Wanders Ronald JA,
Hasenfuß Gerd,
Brügger Britta,
Guan Kaomei,
Rehling Peter
Publication year - 2016
Publication title -
embo molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.923
H-Index - 107
eISSN - 1757-4684
pISSN - 1757-4676
DOI - 10.15252/emmm.201505644
Subject(s) - cardiolipin , succinate dehydrogenase , cardiomyopathy , mitochondrion , mitochondrial respiratory chain , respiratory chain , biology , medicine , endocrinology , microbiology and biotechnology , biochemistry , heart failure , phospholipid , membrane
Barth syndrome ( BTHS ) is a cardiomyopathy caused by the loss of tafazzin, a mitochondrial acyltransferase involved in the maturation of the glycerophospholipid cardiolipin. It has remained enigmatic as to why a systemic loss of cardiolipin leads to cardiomyopathy. Using a genetic ablation of tafazzin function in the BTHS mouse model, we identified severe structural changes in respiratory chain supercomplexes at a pre‐onset stage of the disease. This reorganization of supercomplexes was specific to cardiac tissue and could be recapitulated in cardiomyocytes derived from BTHS patients. Moreover, our analyses demonstrate a cardiac‐specific loss of succinate dehydrogenase ( SDH ), an enzyme linking the respiratory chain with the tricarboxylic acid cycle. As a similar defect of SDH is apparent in patient cell‐derived cardiomyocytes, we conclude that these defects represent a molecular basis for the cardiac pathology in Barth syndrome.