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Complex I and ATP Content Deficiency in Lymphocytes from Friedreich's Ataxia

Published online by Cambridge University Press:  02 December 2014

Mohammad Mehdi Heidari ,
Massoud Houshmand ,
Saman Hosseinkhani ,
Shahriar Nafissi  and
Mehri Khatami
Mohammad Mehdi Heidari
Affiliation:
Genetic Group, Science School, Tarbiat Modares University
Massoud Houshmand*
Affiliation:
Department of Medical Genetic, National Institute for Genetic Engineering and Biotechnology, Special Medical Center
Saman Hosseinkhani
Affiliation:
Biochemical Group Science School, Tarbiat Modares University
Shahriar Nafissi
Affiliation:
Department of Neurology, Medical Science, Tehran University, Tehran, Iran
Mehri Khatami
Affiliation:
Genetic Group, Science School, Tarbiat Modares University
*
Department of Medical Genetic, National Institute for Genetic Engineering and Biotechnology (NIGEB), Tehran, Iran.
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Abstract

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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.

Type
Research Article
Information
Canadian Journal of Neurological Sciences , Volume 36 , Issue 1 , January 2009 , pp. 26 - 31
Copyright
Copyright © The Canadian Journal of Neurological 2009

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