Updated project metadata. S-adenosylmethionine (SAM) is the principle biological methyl group donor for a diverse range of substrates. It is synthesised in the cytosolic methionine cycle and shuttled throughout the cell. The mitochondrial SAM (mitoSAM) pool depends on import through the inner-membrane SAMC and supports the maturation of metabolites and mitochondrial RNAs. Mutations in SAMC in patients cause a severe metabolic crisis, however, the organellar regulation of mitoSAM and the protein methylation landscape within mitochondria are largely unknown. We mapped mitochondrial protein methylation sites in Drosphila and, in a targeted screen, we find that methylated residues are highly conserved between fly, mouse and human. Unexpectedly, many methylation events occur outside of mitochondria, independent of the mitoSAM pool. Our results define the critical role of cytoplasmic SAM production for mitochondrial methylation events and highlight the indirect effect of one-carbon metabolism on cellular bioenergetics.