Complex I and ATP content deficiency in lymphocytes from Friedreich's ataxia.
BACKGROUND
Friedreich's ataxia (FRDA) is an inherited recessive disorder characterized by progressive neurological disability and heart abnormalities. A deficiency in the protein frataxin causes this disease. Frataxin deficiency leads to progressive iron accumulation in mitochondria, excessive free radical production and dysfunction of respiratory chain complexes. The expansion (GAA) repeat in the first intron causes decreased frataxin expression by interfering with transcription.


METHODS
Activity of mitochondrial respiratory chain complex I (measured as NADH ferricyanide reductase) and intracellular ATP measurement was performed on lymphocyte of FRDA patients (n=12) and control subjects (n=25).


RESULTS
Our findings showed that complex I activity and intracellular ATP were significantly reduced (P=0.001) in patients compared with controls and we found strong correlation between complex I activity and intracellular ATP content in FRDA patients (r=0.93; P<0.002). 8.6 and 9.0 kb deletion in mtDNA was detected in 9 patients out of 12 (75%) by multiplex polymerase chain reaction (PCR) and Southern blot analysis.


CONCLUSIONS
This study suggested that a biochemical defect in complex I activity and ATP production, which may be due to iron accumulation in mitochondria, can be involved in age of onset of FRDA.
Heidari
Mohammad Mehdi
MM
Genetic Group, Science School, Tarbiat Modares University, Iran.
Houshmand
Massoud
M
Hosseinkhani
Saman
S
Nafissi
Shahriar
S
Khatami
Mehri
M
D000255:Adenosine Triphosphate / Q000172:deficiency*; D000293:Adolescent; D000328:Adult; D002648:Child; D004272:DNA, Mitochondrial / Q000235:genetics / Q000378:metabolism; D042967:Electron Transport Complex I / Q000172:deficiency*; D005260:Female; D005621:Friedreich Ataxia / Q000235:genetics / Q000276:immunology / Q000473:pathology*; D006801:Humans; D007958:Leukocyte Count; D008214:Lymphocytes / Q000378:metabolism*; D008297:Male; D009247:NADH, NADPH Oxidoreductases / Q000378:metabolism; D013223:Statistics as Topic; D018911:Trinucleotide Repeats; D055815:Young Adult
D004272:DNA, Mitochondrial; D000255:Adenosine Triphosphate; D009247:NADH, NADPH Oxidoreductases; C014227:ferricyanide reductase; D042967:Electron Transport Complex I