title: Biochemistry of cardiomyopathy in the mitochondrial disease Friedreich's ataxia.
abstract: 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.
authors.affiliation: Molecular Pharmacology and Pathology Program, Department of Pathology and Bosch Institute, Blackburn Building, D06, University of Sydney, Sydney, NSW 2006, Australia.
authors.forename: Darius J R
authors.initials: DJ
authors.lastname: Lane
authors.forename: Michael Li-Hsuan
authors.initials: ML
authors.lastname: Huang
authors.forename: Samantha
authors.initials: S
authors.lastname: Ting
authors.forename: Sutharshani
authors.initials: S
authors.lastname: Sivagurunathan
authors.forename: Des R
authors.initials: DR
authors.lastname: Richardson
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D009202:Cardiomyopathies / Q000378:metabolism* / Q000503:physiopathology; D005621:Friedreich Ataxia / Q000378:metabolism* / Q000503:physiopathology; D006801:Humans; D033862:Iron-Binding Proteins / Q000378:metabolism; D028361:Mitochondrial Diseases / Q000378:metabolism* / Q000503:physiopathology; D018384:Oxidative Stress / Q000502:physiology; D000096923:Frataxin
chemical_list: D033862:Iron-Binding Proteins; D000096923:Frataxin