The lower levels of SAM in cytosol was correlated with the lower levels of mtDNA methylation in Down Syndrome (DS) patients25; while, the higher levels of SAM generated due to overexpression of SLC25A26 gene (encoding for the mitochondrial carrier that catalyzes the import of SAM into the mitochondrial matrix), promoted hypermethylation of mtDNA, leading to decreased expression of key respiratory complex subunits, reduction of mitochondrial ATP and release of cytochrome c26. The gene discussed is SLC25A26; the disease is Down syndrome.