{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Curran JE"],"funding":["NIDDK NIH HHS","NCRR NIH HHS","NIMH NIH HHS","NHLBI NIH HHS"],"pagination":["183-90"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC2829432"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["127(2)"],"pubmed_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."],"journal":["Human genetics"],"pubmed_title":["Genetic variation in PARL influences mitochondrial content."],"pmcid":["PMC2829432"],"funding_grant_id":["R01 DK079169","DK079169","C06 RR013556","R37 MH059490","R01 DK071895-03","R01 DK065598-05","R01 DK079169-03","C06 RR013556-01","DK065598","R01 DK071895","R01 MH059490","P01 HL045522","R01 DK065598","DK071895","MH059490","R37 MH059490-12"],"pubmed_authors":["Abraham LJ","Jowett JB","Elliott KS","Walder KR","Johnson MP","Moses EK","Blangero J","Dyer TD","Comuzzie AG","Diepeveen LA","Kerr-Bayles LJ","Collier GR","Curran JE","Kissebah AH"],"additional_accession":[]},"is_claimable":false,"name":"Genetic variation in PARL influences mitochondrial content.","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.","dates":{"release":"2010-01-01T00:00:00Z","publication":"2010 Feb","modification":"2024-11-19T17:30:56Z","creation":"2020-11-07T09:51:09Z"},"accession":"S-EPMC2829432","cross_references":{"pubmed":["19862556"],"doi":["10.1007/s00439-009-0756-0"]}}