| First Author | Dudek J | Year | 2016 |
| Journal | EMBO Mol Med | Volume | 8 |
| Issue | 2 | Pages | 139-54 |
| PubMed ID | 26697888 | Mgi Jnum | J:239991 |
| Mgi Id | MGI:5882168 | Doi | 10.15252/emmm.201505644 |
| Citation | Dudek J, et al. (2016) Cardiac-specific succinate dehydrogenase deficiency in Barth syndrome. EMBO Mol Med 8(2):139-54 |
| abstractText | 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. |
