Genetic variation in PARL influences mitochondrial content
Given their involvement in processes necessary for life, mitochondrial damage and subsequent dysfunction can lead to a wide range of human diseases. Previous studies of both animal models and humans have suggested that presenilins-associated rhomboid-like protein (PARL) is a key regulator of mitocho...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Journal Article |
| Published: |
2010
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| Online Access: | http://hdl.handle.net/20.500.11937/7519 |
| _version_ | 1848745391566094336 |
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| author | Curran, J. Jowett, J. Abraham, L. Diepeveen, L. Elliott, K. Dyer, T. Kerr-Bayles, L. Johnson, M. Comuzzie, A. Moses, Eric Walder, K. Collier, G. Blangero, J. Kissebah, A. |
| author_facet | Curran, J. Jowett, J. Abraham, L. Diepeveen, L. Elliott, K. Dyer, T. Kerr-Bayles, L. Johnson, M. Comuzzie, A. Moses, Eric Walder, K. Collier, G. Blangero, J. Kissebah, A. |
| author_sort | Curran, J. |
| building | Curtin Institutional Repository |
| collection | Online Access |
| description | Given their involvement in processes necessary for life, mitochondrial damage and subsequent dysfunction can lead to a wide range of human diseases. Previous studies of both animal models and humans have suggested that presenilins-associated rhomboid-like protein (PARL) is a key regulator of mitochondrial integrity and function, and plays a role in cellular apoptosis. As a surrogate measure of mitochondrial integrity, we previously measured mitochondrial content in a Caucasian population consisting of large extended pedigrees, with results highlighting a substantial genetic component to this trait. To assess the influence of variation in the PARL gene on mitochondrial content, we re-sequenced 6.5 kb of the gene, identifying 16 SNPs and genotyped these in 1,086 Caucasian individuals, distributed across 170 families. Statistical genetic analysis revealed that one promoter variant, T-191C, exhibited significant effects (after correction for multiple testing) on mitochondrial content levels. Comparison of the transcription factor binding characteristics of the T-191C promoter SNP by EMSA indicates preferential binding of nuclear factors to the T allele, suggesting functional variation in PARL expression. These results suggest that genetic variation within PARL influences mitochondrial abundance and integrity. © 2009 Springer-Verlag. |
| first_indexed | 2025-11-14T06:16:37Z |
| format | Journal Article |
| id | curtin-20.500.11937-7519 |
| institution | Curtin University Malaysia |
| institution_category | Local University |
| last_indexed | 2025-11-14T06:16:37Z |
| publishDate | 2010 |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | curtin-20.500.11937-75192018-03-29T09:05:39Z Genetic variation in PARL influences mitochondrial content Curran, J. Jowett, J. Abraham, L. Diepeveen, L. Elliott, K. Dyer, T. Kerr-Bayles, L. Johnson, M. Comuzzie, A. Moses, Eric Walder, K. Collier, G. Blangero, J. Kissebah, A. Given their involvement in processes necessary for life, mitochondrial damage and subsequent dysfunction can lead to a wide range of human diseases. Previous studies of both animal models and humans have suggested that presenilins-associated rhomboid-like protein (PARL) is a key regulator of mitochondrial integrity and function, and plays a role in cellular apoptosis. As a surrogate measure of mitochondrial integrity, we previously measured mitochondrial content in a Caucasian population consisting of large extended pedigrees, with results highlighting a substantial genetic component to this trait. To assess the influence of variation in the PARL gene on mitochondrial content, we re-sequenced 6.5 kb of the gene, identifying 16 SNPs and genotyped these in 1,086 Caucasian individuals, distributed across 170 families. Statistical genetic analysis revealed that one promoter variant, T-191C, exhibited significant effects (after correction for multiple testing) on mitochondrial content levels. Comparison of the transcription factor binding characteristics of the T-191C promoter SNP by EMSA indicates preferential binding of nuclear factors to the T allele, suggesting functional variation in PARL expression. These results suggest that genetic variation within PARL influences mitochondrial abundance and integrity. © 2009 Springer-Verlag. 2010 Journal Article http://hdl.handle.net/20.500.11937/7519 10.1007/s00439-009-0756-0 restricted |
| spellingShingle | Curran, J. Jowett, J. Abraham, L. Diepeveen, L. Elliott, K. Dyer, T. Kerr-Bayles, L. Johnson, M. Comuzzie, A. Moses, Eric Walder, K. Collier, G. Blangero, J. Kissebah, A. Genetic variation in PARL influences mitochondrial content |
| title | Genetic variation in PARL influences mitochondrial content |
| title_full | Genetic variation in PARL influences mitochondrial content |
| title_fullStr | Genetic variation in PARL influences mitochondrial content |
| title_full_unstemmed | Genetic variation in PARL influences mitochondrial content |
| title_short | Genetic variation in PARL influences mitochondrial content |
| title_sort | genetic variation in parl influences mitochondrial content |
| url | http://hdl.handle.net/20.500.11937/7519 |