The muscle-specific microRNA miR-1 stimulates translation of various transcripts encoded by mitochondrial DNA, while repressing its nuclear DNA-encoded targets in the cytoplasm, report Zhang and colleagues. The observed effect is dependent on specific base-pairing between miR-1 and its target transcripts, as well as on the presence of Argonaute 2 (AGO2), which was shown by crosslinking and immunoprecipitation coupled with deep sequencing (CLIP–seq) to bind to the transcripts directly. The authors propose that AGO2 functions as a key mitochondrial translation initiation factor to facilitate ribosome–mRNA interactions.