Genetic variation in PARL influences mitochondrial content

Joanne E. Curran, Jeremy B.M. Jowett, Lawrence J. Abraham, Luke A. Diepeveen, Katherine S. Elliott, Thomas D. Dyer, Lyndal J. Kerr-Bayles, Matthew P. Johnson, Anthony G. Comuzzie, Eric K. Moses, Ken R. Walder, Gregory R. Collier, John Blangero, Ahmed H. Kissebah

Research output: Contribution to journalArticlepeer-review

15 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)183-190
Number of pages8
JournalHuman Genetics
Issue number2
StatePublished - 2010
Externally publishedYes

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)


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