mtDNA-CN loci influence mitochondrial gene expression and heteroplasmy
We postulated that mtDNA-CN loci may regulate copy number by inducing changes in expression of genes that are directly transcribed from mtDNA. Ali et al. Recently conducted a GWAS to identify nuclear genetic variants associated with variation in mtDNA-encoded gene expression (i.e. mt-eQTLs). Nonsynonymous variants in LONP1 (rs11085147) and TBRG4 (rs230469). Nominally associated mtDNA-CN loci were also observed to influence MT gene expression including intronic variants in both PNPTand LRPPRC.
- Moreover, the direction of effect estimates between mtDNA-CN
- and mt-eQTLs varied depending on gene and tissue context.
- Altogether, such findings imply that some mtDNA-CN loci may
- egulate mtDNA-CN by influencing mitochondrial gene expression.
Although differences in mitochondrial gene expression may be a consequence rather than a cause of variable mtDNA-CN, the analysis performed by Ali et al (2019) was corrected for factors associated with global changes in the mitochondrial transcriptome.