Cardiolipin deficiency in Barth syndrome is not associated with increased superoxide/H 2 O 2 production in heart and skeletal muscle mitochondria

FEBS Letters

article

Renata L. S. Goncalves¹  Michael Schlame²  Alexander Bartelt¹  Martin D. Brand⁴  Gökhan S. Hotamışlıgil¹ 

[1]Sabri Ülker Center for Metabolic Research and Department of Molecular Metabolism, Harvard T.H. Chan School of Public Health

[2]Departments of Anesthesiology and Cell Biology, New York University School of Medicine

[3]Institute for Cardiovascular Prevention ,(IPEK), Ludwig-Maximilians-University

[4]Buck Institute for Research on Aging

[5]Broad Institute of MIT and Harvard

关键词: Barth syndrome;    cardiomyopathy;    ‘ex vivo’ rate of superoxide/H2O2 production;    mitochondria;    mitochondrial reactive oxygen species;    superoxide/H2O2;    tafazzin;    tazkd mice;   

DOI  :  10.1002/1873-3468.13973

来源: John Wiley & Sons Ltd.

【 摘 要 】

Barth syndrome (BTHS) is a rare X-linked genetic disorder caused by mutations in the gene encoding the transacylase tafazzin and characterized by loss of cardiolipin and severe cardiomyopathy. Mitochondrial oxidants have been implicated in the cardiomyopathy in BTHS. Eleven mitochondrial sites produce superoxide/hydrogen peroxide (H 2 O 2 ) at significant rates. Which of these sites generate oxidants at excessive rates in BTHS is unknown. Here, we measured the maximum capacity of superoxide/H 2 O 2 production from each site and the ex vivo rate of superoxide/H 2 O 2 production in the heart and skeletal muscle mitochondria of the tafazzin knockdown mice (tazkd) from 3 to 12 months of age. Despite reduced oxidative capacity, superoxide/H 2 O 2 production was indistinguishable between tazkd mice and wild-type littermates. These observations raise questions about the involvement of mitochondrial oxidants in BTHS pathology.

【 授权许可】

Unknown