title: Blood cells from Friedreich ataxia patients harbor frataxin deficiency without a loss of mitochondrial function.
abstract: Friedreich ataxia (FRDA) is an autosomal recessive neurodegenerative disorder caused by GAA triplet expansions or point mutations in the FXN gene on chromosome 9q13. The gene product called frataxin, a mitochondrial protein that is severely reduced in FRDA patients, leads to mitochondrial iron accumulation, Fe-S cluster deficiency and oxidative damage. The tissue specificity of this mitochondrial disease is complex and poorly understood. While frataxin is ubiquitously expressed, the cellular phenotype is most severe in neurons and cardiomyocytes. Here, we conducted comprehensive proteomic, metabolic and functional studies to determine whether subclinical abnormalities exist in mitochondria of blood cells from FRDA patients. Frataxin protein levels were significantly decreased in platelets and peripheral blood mononuclear cells from FRDA patients. Furthermore, the most significant differences associated with frataxin deficiency in FRDA blood cell mitochondria were the decrease of two mitochondrial heat shock proteins. We did not observe profound changes in frataxin-targeted mitochondrial proteins or mitochondrial functions or an increase of apoptosis in peripheral blood cells, suggesting that functional defects in these mitochondria are not readily apparent under resting conditions in these cells.
authors.affiliation: Children's Hospital of Philadelphia Research Institute, Children's Hospital of Philadelphia and University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Mary A
authors.initials: MA
authors.lastname: Selak
authors.forename: Elise
authors.initials: E
authors.lastname: Lyver
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Micklow
authors.forename: Eric C
authors.initials: EC
authors.lastname: Deutsch
authors.forename: Ozlem
authors.initials: O
authors.lastname: Onder
authors.forename: Nur
authors.initials: N
authors.lastname: Selamoglu
authors.forename: Claire
authors.initials: C
authors.lastname: Yager
authors.forename: Simon
authors.initials: S
authors.lastname: Knight
authors.forename: Martin
authors.initials: M
authors.lastname: Carroll
authors.forename: Fevzi
authors.initials: F
authors.lastname: Daldal
authors.forename: Andrew
authors.initials: A
authors.lastname: Dancis
authors.forename: David R
authors.initials: DR
authors.lastname: Lynch
authors.forename: Jean-Emmanuel
authors.initials: JE
authors.lastname: Sarry
mesh_terms: D000328:Adult; D015153:Blotting, Western; D016022:Case-Control Studies; D015180:Electrophoresis, Gel, Two-Dimensional; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D005621:Friedreich Ataxia / Q000097:blood*; D006801:Humans; D033862:Iron-Binding Proteins / Q000235:genetics*; D008297:Male; D013058:Mass Spectrometry; D008928:Mitochondria / Q000502:physiology*; D000096923:Frataxin
chemical_list: D033862:Iron-Binding Proteins; D000096923:Frataxin