Aim-less translation: loss of Saccharomyces cerevisiae mitochondrial translation initiation factor mIF3/Aim23 leads to unbalanced protein synthesis

Abstract

The mitochondrial genome almost exclusively encodes a handful of transmembrane constituents of the oxidative phosphorylation (OXPHOS) system. Coordinated expression of these genes ensures the correct stoichiometry of the system’s components. Translation initiation in mitochondria is assisted by two general initiation factors mIF2 and mIF3, orthologues of which in bacteria are indispensible for protein synthesis and viability. mIF3 was thought to be absent in Saccharomyces cerevisiae until we recently identified mitochondrial protein Aim23 as the missing orthologue. Here we show that, surprisingly, loss of mIF3/Aim23 in S. cerevisiae does not indiscriminately abrogate mitochondrial translation but rather causes an imbalance in protein production: the rate of synthesis of the Atp9 subunit of F1F0 ATP synthase (complex V) is increased, while expression of Cox1, Cox2 and Cox3 subunits of cytochrome c oxidase (complex IV) is repressed. Our results provide one more example of deviation of mitochondrial translation from its bacterial origins.

Initiation Factor 3 is Dispensable For Mitochondrial Translation in Cultured Human Cells

“…This is not surprising, as respiration relies heavily on mitochondria. This was observed for AIM23, the homolog of IF3 in yeast mitochondria: the strain bearing null deletion had a pronounced lag phase growing in media with non-fermentable carbon sources 14 . To assess the respiratory function of MTIF3 knock-out cells, we measured their oxygen consumption in two modes, namely coupled and uncoupled.…”

“…It is well-known that IF3 plays a central role in the ribosomal cycle and the corresponding gene is essential in prokaryotes 13 . On the other hand, the deletion of its homolog in yeast S. cerevisiae mitochondria, AIM23, did not block mitochondrial translation, but brought significant "imbalance" in protein synthesis 14 . Having human cell lines with MTIF3 deficiency in our hands, it was tempting to explore what happens with the human mitochondrial translation system upon the deletion of the IF3 homolog.…”

Schizosaccharomyces pombe Mti2 and Mti3 act in conjunction during mitochondrial translation initiation

“…However, the Δ aim23 mutant exhibits defects that are not observed in the Δ mti2 mutant. First, deletion of aim23 but not mti3 significantly impairs the growth of yeast cells on respiratory medium requiring mitochondrial respiration . Second, deletion of aim23 leads to an imbalance of mitochondrial protein synthesis .…”

“…First, deletion of aim23 but not mti3 significantly impairs the growth of yeast cells on respiratory medium requiring mitochondrial respiration . Second, deletion of aim23 leads to an imbalance of mitochondrial protein synthesis . However, deletion of mti3 has no apparent effect on mitochondrial translation.…”

“…Both NTE and CTE are unique characteristics of mammalian mtIF3. Unlike mammalian mtIF3, S. cerevisiae mtIF3 (Aim23, also called Mif3) appears to be dispensable for mitochondrial translation .…”