Cardiac-specific succinate dehydrogenase deficiency in Barth syndrome
2016 | journal article; research paper
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- Authors
- Dudek, Jan ; Cheng, I-Fen ; 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
- 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.
- Issue Date
- 2016
- Journal
- EMBO Molecular Medicine
- Project
- SFB 1002: Modulatorische Einheiten bei Herzinsuffizienz
SFB 1002 | A06: Molekulare Grundlagen mitochondrialer Kardiomyopathien - Working Group
- RG Guan (Application of patient-specific induced pluripotent stem cells in disease modelling)
RG Hasenfuß (Transition zur Herzinsuffizienz)
RG Rehling (Mitochondrial Protein Biogenesis)
RG Toischer (Kardiales Remodeling) - ISSN
- 1757-4676; 1757-4684
- Language
- English