FRDA (Friedreich's ataxia) is a debilitating mitochondrial disorder leading to neural and cardiac degeneration, which is caused by a mutation in the frataxin gene that leads to decreased frataxin expression. The most common cause of death in FRDA patients is heart failure, although it is not known how the deficiency in frataxin potentiates the observed cardiomyopathy. The major proposed biochemical mechanisms for disease pathogenesis and the origins of heart failure in FRDA involve metabolic perturbations caused by decreased frataxin expression. Additionally, recent data suggest that low frataxin expression in heart muscle of conditional frataxin knockout mice activates an integrated stress response that contributes to and/or exacerbates cardiac hypertrophy and the loss of cardiomyocytes. The elucidation of these potential mechanisms will lead to a more comprehensive understanding of the pathogenesis of FRDA, and will contribute to the development of better treatments and therapeutics.
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August 2013
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Review Article|
July 12 2013
Biochemistry of cardiomyopathy in the mitochondrial disease Friedreich's ataxia
Darius J. R. Lane
;
Darius J. R. Lane
1
1Molecular Pharmacology and Pathology Program, Department of Pathology and Bosch Institute, Blackburn Building (D06), University of Sydney, Sydney, NSW 2006, Australia
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Michael Li-Hsuan Huang
;
Michael Li-Hsuan Huang
1
1Molecular Pharmacology and Pathology Program, Department of Pathology and Bosch Institute, Blackburn Building (D06), University of Sydney, Sydney, NSW 2006, Australia
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Samantha Ting
;
Samantha Ting
1Molecular Pharmacology and Pathology Program, Department of Pathology and Bosch Institute, Blackburn Building (D06), University of Sydney, Sydney, NSW 2006, Australia
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Sutharshani Sivagurunathan
;
Sutharshani Sivagurunathan
1Molecular Pharmacology and Pathology Program, Department of Pathology and Bosch Institute, Blackburn Building (D06), University of Sydney, Sydney, NSW 2006, Australia
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Des R. Richardson
Des R. Richardson
2
1Molecular Pharmacology and Pathology Program, Department of Pathology and Bosch Institute, Blackburn Building (D06), University of Sydney, Sydney, NSW 2006, Australia
2To whom correspondence should be addressed (email d.richardson@med.usyd.edu.au).
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Biochem J (2013) 453 (3): 321–336.
Article history
Received:
January 14 2013
Revision Received:
April 12 2013
Accepted:
May 15 2013
Citation
Darius J. R. Lane, Michael Li-Hsuan Huang, Samantha Ting, Sutharshani Sivagurunathan, Des R. Richardson; Biochemistry of cardiomyopathy in the mitochondrial disease Friedreich's ataxia. Biochem J 1 August 2013; 453 (3): 321–336. doi: https://doi.org/10.1042/BJ20130079
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