Methionine on the rise: how mitochondria changed their codon usage

The tRNA specific for methionine ( tRNA M et ) of human mitochondria contains a formyl‐cytosine at the wobble position of the anticodon to facilitate its binding to AUG , AUA and (in one instance) to AUU . In this issue of The EMBO Journal , Haag et al identify a two‐step enzyme pathway facilitating the modification of the tRNA . Sequential reactions of the methyltransferase NSUN 3 and the dioxygenase ALKBH 1/ ABH 1 are important to render the tRNA as able to recognize the non‐canonical methionine codons AUA and AUU s, a property critical for efficient protein synthesis in human mitochondria.