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- Title
Genetic variation in PARL influences mitochondrial content.
- Authors
Curran, Joanne E.; Jowett, Jeremy B. M.; Abraham, Lawrence J.; Diepeveen, Luke A.; Elliott, Katherine S.; Dyer, Thomas D.; Kerr-Bayles, Lyndal J.; Johnson, Matthew P.; Comuzzie, Anthony G.; Moses, Eric K.; Walder, Ken R.; Collier, Gregory R.; Blangero, John; Kissebah, Ahmed H.
- Abstract
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.
- Subjects
MITOCHONDRIAL pathology; MEMBRANE proteins; TRANSCRIPTION factors; APOPTOSIS; GENETICS
- Publication
Human Genetics, 2010, Vol 127, Issue 2, p183
- ISSN
0340-6717
- Publication type
Article
- DOI
10.1007/s00439-009-0756-0