Gene expression profiling of mitochondrial oxidative phosphorylation (OXPHOS) complex I in Friedreich ataxia (FRDA) patients.
Friedreich ataxia (FRDA) is the most frequent progressive autosomal recessive disorder associated with unstable expansion of GAA trinucleotide repeats in the first intron of the FXN gene, which encodes for the mitochondrial frataxin protein. The number of repeats correlates with disease severity, where impaired transcription of the FXN gene results in reduced expression of the frataxin protein. Gene expression studies provide insights into disease pathogenicity and identify potential biomarkers, an important goal of translational research in neurodegenerative diseases. Here, using real-time PCR (RT-PCR), the expression profiles of mitochondrial (mtDNA) and nuclear DNA (nDNA) genes that encode for the mitochondrial subunits of respiratory oxidative phosphorylation (OXPHOS) complex I in the blood panels of 21 FRDA patients and 24 healthy controls were investigated. Here, the expression pattern of mtDNA-encoded complex I subunits was distinctly different from the expression pattern of nDNA-encoded complex I subunits, where significant (p<0.05) down-regulation of the mitochondrial ND2, ND4L, and ND6 complex I genes, compared to controls, were observed. In addition, the expression pattern of one nDNA-encoded gene, NDUFA1, was significantly (p<0.05) down-regulated compared to control. These findings suggest, for the first time, that the regulation of complex I subunit expression in FRDA is complex, rather than merely being a reflection of global co-regulation, and may provide important clues toward novel therapeutic strategies for FRDA and mitochondrial complex I deficiency.
Department of Molecular Genetics, Tarbiat Modares University, Tehran, Iran.
Mohammad Hossein
MH
Salehi
Department of Pharmacy, Faculty of Medicine, University of Malaya (UM), Kuala Lumpur, Malaysia.
Behnam
B
Kamalidehghan
Department of Medical Genetics, National Institute for Genetic Engineering and Biotechnology, Tehran, Iran; Department of Medical Genetics, Special Medical Center, Tehran, Iran.
Massoud
M
Houshmand
Department of Preclinical Sciences, Faculty of Veterinary Medicine, Universiti Putra Malaysia, Selangor, Malaysia; Institute of Tropical Agriculture, Universiti Putra Malaysia, Selangor, Malaysia.
Goh
G
Yong Meng
Department of Molecular Genetics, Tarbiat Modares University, Tehran, Iran.
Majid
M
Sadeghizadeh
Department of Medical Genetics, Special Medical Center, Tehran, Iran.
Omid
O
Aryani
Department of Neurology, Tehran University of Medical Sciences, Shariati Hospital, Tehran, Iran.
Shahriar
S
Nafissi
D000293:Adolescent; D000328:Adult; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D042967:Electron Transport Complex I / Q000235:genetics*; D005260:Female; D005621:Friedreich Ataxia / Q000175:diagnosis / Q000235:genetics*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D050259:Genes, Mitochondrial; D006801:Humans; D008297:Male; D055815:Young Adult
D042967:Electron Transport Complex I