title: Cardiac-specific succinate dehydrogenase deficiency in Barth syndrome.
abstract: 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.
authors.affiliation: Department of Cellular Biochemistry, University Medical Center Göttingen, Göttingen, Germany.
authors.forename: Jan
authors.initials: J
authors.lastname: Dudek
authors.affiliation: Department of Cellular Biochemistry, University Medical Center Göttingen, Göttingen, Germany Department of Cardiology and Pneumology, University Medical Center Göttingen, Göttingen, Germany.
authors.forename: I-Fen
authors.initials: IF
authors.lastname: Cheng
authors.affiliation: Department of Cellular Biochemistry, University Medical Center Göttingen, Göttingen, Germany.
authors.forename: Arpita
authors.initials: A
authors.lastname: Chowdhury
authors.affiliation: Heidelberg University Biochemistry Center, University Heidelberg, Heidelberg, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Wozny
authors.affiliation: Department of Cellular Biochemistry, University Medical Center Göttingen, Göttingen, Germany.
authors.forename: Martina
authors.initials: M
authors.lastname: Balleininger
authors.affiliation: Department of Cellular Biochemistry, University Medical Center Göttingen, Göttingen, Germany.
authors.forename: Robert
authors.initials: R
authors.lastname: Reinhold
authors.affiliation: Department of Cellular Biochemistry, University Medical Center Göttingen, Göttingen, Germany.
authors.forename: Silke
authors.initials: S
authors.lastname: Grunau
authors.affiliation: Department of Cellular Biochemistry, University Medical Center Göttingen, Göttingen, Germany.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Callegari
authors.affiliation: Department of Cardiology and Pneumology, University Medical Center Göttingen, Göttingen, Germany German Center for Cardiovascular Research (DZHK), Göttingen, Germany.
authors.forename: Karl
authors.initials: K
authors.lastname: Toischer
authors.affiliation: Departments of Clinical Chemistry and Pediatrics, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Ronald Ja
authors.initials: RJ
authors.lastname: Wanders
authors.affiliation: Department of Cardiology and Pneumology, University Medical Center Göttingen, Göttingen, Germany German Center for Cardiovascular Research (DZHK), Göttingen, Germany Heart Research Center Göttingen, Göttingen, Germany.
authors.forename: Gerd
authors.initials: G
authors.lastname: Hasenfuß
authors.affiliation: Heidelberg University Biochemistry Center, University Heidelberg, Heidelberg, Germany.
authors.forename: Britta
authors.initials: B
authors.lastname: Brügger
authors.affiliation: Department of Cardiology and Pneumology, University Medical Center Göttingen, Göttingen, Germany German Center for Cardiovascular Research (DZHK), Göttingen, Germany Heart Research Center Göttingen, Göttingen, Germany.
authors.forename: Kaomei
authors.initials: K
authors.lastname: Guan
authors.affiliation: Department of Cellular Biochemistry, University Medical Center Göttingen, Göttingen, Germany Heart Research Center Göttingen, Göttingen, Germany Max Planck Institute for Biophysical Chemistry, Göttingen, Germany peter.rehling@medizin.uni-goettingen.de.
authors.forename: Peter
authors.initials: P
authors.lastname: Rehling
mesh_terms: D000818:Animals; D056889:Barth Syndrome / Q000473:pathology*; D002478:Cells, Cultured; D004195:Disease Models, Animal; D006801:Humans; D051379:Mice; D013385:Succinate Dehydrogenase / Q000172:deficiency*
chemical_list: D013385:Succinate Dehydrogenase
keywords: Barth syndrome; cardiolipin; mitochondria; respiratory chain; succinate dehydrogenase