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, wh...
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| Format: | Article |
| Language: | English |
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Public Library of Science
2014
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| Online Access: | http://psasir.upm.edu.my/id/eprint/37748/ http://psasir.upm.edu.my/id/eprint/37748/1/journal.pone.0094069.pdf |
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| author | Salehi, Mohammad Hossein Kamalidehghan, Behnam Houshmand, Massoud Goh, Yong Meng Sadeghizadeh, Majid Aryani, Omid Nafissi, Shahriar |
| author_facet | Salehi, Mohammad Hossein Kamalidehghan, Behnam Houshmand, Massoud Goh, Yong Meng Sadeghizadeh, Majid Aryani, Omid Nafissi, Shahriar |
| author_sort | Salehi, Mohammad Hossein |
| building | UPM Institutional Repository |
| collection | Online Access |
| description | 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. |
| first_indexed | 2025-11-15T09:38:31Z |
| format | Article |
| id | upm-37748 |
| institution | Universiti Putra Malaysia |
| institution_category | Local University |
| language | English |
| last_indexed | 2025-11-15T09:38:31Z |
| publishDate | 2014 |
| publisher | Public Library of Science |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | upm-377482016-04-22T03:32:06Z http://psasir.upm.edu.my/id/eprint/37748/ Gene expression profiling of mitochondrial oxidative phosphorylation (OXPHOS) complex I in Friedreich ataxia (FRDA) patients Salehi, Mohammad Hossein Kamalidehghan, Behnam Houshmand, Massoud Goh, Yong Meng Sadeghizadeh, Majid Aryani, Omid Nafissi, Shahriar 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. Public Library of Science 2014-04 Article PeerReviewed application/pdf en http://psasir.upm.edu.my/id/eprint/37748/1/journal.pone.0094069.pdf Salehi, Mohammad Hossein and Kamalidehghan, Behnam and Houshmand, Massoud and Goh, Yong Meng and Sadeghizadeh, Majid and Aryani, Omid and Nafissi, Shahriar (2014) Gene expression profiling of mitochondrial oxidative phosphorylation (OXPHOS) complex I in Friedreich ataxia (FRDA) patients. PLOS ONE, 9 (4). art. no. e94069. pp. 1-10. ISSN 1932-6203 10.1371/journal.pone.0094069 |
| spellingShingle | Salehi, Mohammad Hossein Kamalidehghan, Behnam Houshmand, Massoud Goh, Yong Meng Sadeghizadeh, Majid Aryani, Omid Nafissi, Shahriar Gene expression profiling of mitochondrial oxidative phosphorylation (OXPHOS) complex I in Friedreich ataxia (FRDA) patients |
| title | Gene expression profiling of mitochondrial oxidative phosphorylation (OXPHOS) complex I in Friedreich ataxia (FRDA) patients |
| title_full | Gene expression profiling of mitochondrial oxidative phosphorylation (OXPHOS) complex I in Friedreich ataxia (FRDA) patients |
| title_fullStr | Gene expression profiling of mitochondrial oxidative phosphorylation (OXPHOS) complex I in Friedreich ataxia (FRDA) patients |
| title_full_unstemmed | Gene expression profiling of mitochondrial oxidative phosphorylation (OXPHOS) complex I in Friedreich ataxia (FRDA) patients |
| title_short | Gene expression profiling of mitochondrial oxidative phosphorylation (OXPHOS) complex I in Friedreich ataxia (FRDA) patients |
| title_sort | gene expression profiling of mitochondrial oxidative phosphorylation (oxphos) complex i in friedreich ataxia (frda) patients |
| url | http://psasir.upm.edu.my/id/eprint/37748/ http://psasir.upm.edu.my/id/eprint/37748/ http://psasir.upm.edu.my/id/eprint/37748/1/journal.pone.0094069.pdf |