Unknown

Dataset Information

0

Genetic variation in PARL influences mitochondrial content.


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.

SUBMITTER: Curran JE 

PROVIDER: S-EPMC2829432 | biostudies-literature | 2010 Feb

REPOSITORIES: biostudies-literature

altmetric image

Publications


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 consist  ...[more]

Similar Datasets

| S-EPMC6282592 | biostudies-literature
| S-EPMC7915608 | biostudies-literature
| S-EPMC3033179 | biostudies-literature
| S-EPMC7966987 | biostudies-literature
2013-08-12 | GSE46949 | GEO
2008-02-13 | GSE7756 | GEO
2013-08-12 | E-GEOD-46949 | biostudies-arrayexpress
2016-02-16 | GSE77905 | GEO
2016-02-16 | E-GEOD-77905 | biostudies-arrayexpress
| S-EPMC4395341 | biostudies-literature