Importantly, numerous studies report a correlation between DNA methylation of the PGC-1α promoter and PGC-1α transcription, mtDNA copy number and metabolic disease (Barrès et al., 2009; Sookoian et al., 2010; Heinonen et al., 2015; Kresovich et al., 2018), suggesting that DNA methylation regulates PGC-1α-driven mitochondrial biogenesis. Here, PPARGC1A is linked to metabolic disease.