title: Complex I and ATP content deficiency in lymphocytes from Friedreich's ataxia.
abstract: 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.
authors.affiliation: Genetic Group, Science School, Tarbiat Modares University, Iran.
authors.forename: Mohammad Mehdi
authors.initials: MM
authors.lastname: Heidari
authors.forename: Massoud
authors.initials: M
authors.lastname: Houshmand
authors.forename: Saman
authors.initials: S
authors.lastname: Hosseinkhani
authors.forename: Shahriar
authors.initials: S
authors.lastname: Nafissi
authors.forename: Mehri
authors.initials: M
authors.lastname: Khatami
mesh_terms: 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
chemical_list: D004272:DNA, Mitochondrial; D000255:Adenosine Triphosphate; D009247:NADH, NADPH Oxidoreductases; C014227:ferricyanide reductase; D042967:Electron Transport Complex I