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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 o...

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Main Authors: Dudek, Jan (Author) , Cheng, I-Fen (Author) , Chowdhury, Arpita (Author) , Wozny, Katharina (Author) , Balleininger, Martina (Author) , Reinhold, Robert (Author) , Grunau, Silke (Author) , Callegari, Sylvie (Author) , Toischer, Karl (Author) , Wanders, Ronald JA (Author) , Hasenfuß, Gerd (Author) , Brügger, Britta (Author) , Guan, Kaomei (Author) , Rehling, Peter (Author)
Format: Article (Journal)
Language:English
Published: 2016
In: EMBO molecular medicine
Year: 2015, Volume: 8, Issue: 2, Pages: 139-154
ISSN:1757-4684
DOI:10.15252/emmm.201505644
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.15252/emmm.201505644
Verlag, lizenzpflichtig, Volltext: https://www.embopress.org/doi/full/10.15252/emmm.201505644
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Author Notes:Jan Dudek, I-Fen Cheng, Arpita Chowdhury, Katharina Wozny, Martina Balleininger, Robert Reinhold, Silke Grunau, Sylvie Callegari, Karl Toischer, Ronald JA Wanders, Gerd Hasenfuß, Britta Brügger, Kaomei Guan & Peter Rehling
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Summary: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.
Item Description:Published online 23 December 2015
Gesehen am 28.04.2020
Physical Description:Online Resource
ISSN:1757-4684
DOI:10.15252/emmm.201505644

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