Mitochondrial impairment of human muscle in Friedreich ataxia in vivo.
Friedreich ataxia occurs due to mutations in the gene encoding the mitochondrial protein frataxin. This (31)P magnetic resonance spectroscopy study on the calf muscle of Friedreich ataxia patients provides in vivo evidence of a severe impairment of mitochondrial function. Mitochondrial adenosine triphosphate resynthesis was studied by means of the post-exercise recovery of phosphocreatine. After ischemic exercise in calf muscles of all patients, phosphocreatine recovery was dramatically delayed. Time constants of recovery correlated with mutations of the frataxin gene, the age of the patients, and disease duration. (31)P magnetic resonance spectroscopy represents the first expedient tool for monitoring therapeutic trials in Friedreich ataxia non-invasively.
Vorgerd
M
M
Department of Neurology, Kliniken Bergmannsheil, Ruhr University Bochum, Bürkle-de-la-Camp-Platz 1, 44789, Bochum, Germany.
Schöls
L
L
Hardt
C
C
Ristow
M
M
Epplen
J T
JT
Zange
J
J
D000255:Adenosine Triphosphate / Q000096:biosynthesis; D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000483:Alleles; D005080:Exercise Test; D005260:Female; D005621:Friedreich Ataxia / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D033862:Iron-Binding Proteins; D007537:Isometric Contraction; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008875:Middle Aged; D008931:Mitochondria, Muscle / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism*; D020388:Muscular Dystrophy, Duchenne / Q000378:metabolism; D010725:Phosphocreatine / Q000378:metabolism; D010759:Phosphorus Isotopes / Q000032:analysis; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics; D018911:Trinucleotide Repeats / Q000235:genetics; D000096923:Frataxin
D000255:Adenosine Triphosphate; D033862:Iron-Binding Proteins; D010725:Phosphocreatine; D010759:Phosphorus Isotopes; D017853:Phosphotransferases (Alcohol Group Acceptor); D000096923:Frataxin