A single mammalian mitochondrial translation initiation factor functionally replaces two bacterial factors

Abstract

The mechanism of translation in eubacteria and organelles is thought to be similar. In eubacteria, the three initiation factors IF1, IF2, and IF3 are vital. Although the homologs of IF2 and IF3 are found in mammalian mitochondria, an IF1 homolog has never been detected. Here, we show that bovine mitochondrial IF2 (IF2_mt) complements E. coli containing a deletion of the IF2 gene (E. coli δ infB). We find that IF1 is no longer essential in an IF2_mt-supported E. coli δ infB strain. Furthermore, biochemical and molecular modeling data show that a conserved insertion of 37 amino acids in the IF2_mt substitutes for the function of IF1. Deletion of this insertion from IF2_mt supports E. coli for the essential function of IF2. However, in this background, IF1 remains essential. These observations provide strong evidence that a single factor (IF2_mt) in mammalian mitochondria performs the functions of two eubacterial factors, IF1 and IF2.