Mitochondrial translation initiation

Translation initiates with the mitochondrial mRNA binding the 28S subunit:MTIF3 (28S subunit:IF-3Mt, 28S subunit:IF3mt) complex together with MTIF2:GTP (IF-2Mt:GTP, IF2mt:GTP) (reviewed in Christian and Spremulli 2012, Kuzmenko et al. 2014). As inferred from bovine homologs, the 28S subunit, 39S subunit, and 55S holoribosome associate with the matrix-side face of the inner membrane and the translation products are inserted into the inner membrane as translation occurs. Mitochondrial mRNAs have either no untranslated leader or short leaders of 1-3 nucleotides, with the exception of the 2 bicistronic transcripts, RNA7 and RNA14, which have overlapping orfs that encode ND4L/ND4 and ATP8/ATP6 respectively.. Binding of N-formylmethionine-tRNA to the start codon results in a stable complex between the mRNA and the 28S subunit while absence of a start codon at the 5' end of the mRNA causes the mRNA to slide though the 28S subunit and eventually dissociate. The 39S subunit then binds the 28S subunit:mRNA complex, GTP is hydrolyzed, and the initiation factors MTIF3 and MTIF2:GDP dissociate.

Summary from Reactome (R-HSA-5368286), read 2026-09-23.