Johnson 2018 J Mol Cell Cardiol

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Johnson JM, Ferrara PJ, Verkerke ARP, Coleman CB, Wentzler EJ, Neufer PD, Kew KA, de Castro Brás LE, Funai K (2018) Targeted overexpression of catalase to mitochondria does not prevent cardioskeletal myopathy in Barth syndrome. J Mol Cell Cardiol 121:94-102.

» PMID: 30008435

Johnson JM, Ferrara PJ, Verkerke ARP, Coleman CB, Wentzler EJ, Neufer PD, Kew KA, de Castro Bras LE, Funai K (2018) J Mol Cell Cardiol

Abstract: Barth Syndrome (BTHS) is an X-linked recessive disorder characterized by cardiomyopathy and muscle weakness. The underlying cause of BTHS is a mutation in the tafazzin (TAZ) gene, a key enzyme of cardiolipin biosynthesis. The lack of CL arising from loss of TAZ function results in destabilization of the electron transport system, promoting oxidative stress that is thought to contribute to development of cardioskeletal myopathy. Indeed, in vitro studies demonstrate that mitochondria-targeted antioxidants improve contractile capacity in TAZ-deficient cardiomyocytes. The purpose of the present study was to determine if resolving mitochondrial oxidative stress would be sufficient to prevent cardiomyopathy and skeletal myopathy in vivo using a mouse model of BTHS. To this end we crossed mice that overexpress catalase in the mitochondria (MCAT mice) with TAZ-deficient mice (TAZKD) to produce TAZKD mice that selectively overexpress catalase in the mitochondria (TAZKD+MCAT mice). TAZKD+MCAT mice exhibited decreased mitochondrial H2O2 emission and lipid peroxidation compared to TAZKD littermates, indicating decreased oxidative stress. Despite the improvements in oxidative stress, TAZKD+MCAT mice developed cardiomyopathy and mild muscle weakness similar to TAZKD littermates. These findings indicate that resolving oxidative stress is not sufficient to suppress cardioskeletal myopathy associated with BTHS.

Keywords: Barth syndrome, Cardiomyopathy, Mitochondria, Oxidative stress, Reactive oxygen species Bioblast editor: Plangger M O2k-Network Lab: US NC Greenville Neufer PD


Labels: MiParea: Respiration  Pathology: Myopathy 

Organism: Mouse  Tissue;cell: Heart, Skeletal muscle  Preparation: Isolated mitochondria 


Coupling state: OXPHOS, ET  Pathway: F, N, S, NS  HRR: Oxygraph-2k 

Labels, 2018-08