Approaches to Humanization of Mitochondrial Proteins in on the Example of Replacing the Yeast Mitochondrial Translation Termination Factor Mrf1 With Its Human Homologs

Mitochondrial translation is a highly specialized process of synthesizing mitochondrically encoded proteins, mainly the components of the oxidative phosphorylation system. It involves four key stages: initiation, elongation, termination, and recycling of mitochondrial ribosomes. Each of these stages is regulated by a specific set of translation factors, most of which are encoded by the nuclear genome and imported into mitochondria. The termination of mitochondrial translation in yeast () is carried out by the MRF1 release factor. This nuclear-encoded factor is crucial for ensuring accurate protein synthesis within the organelle, as it recognizes stop codons and facilitates the release of completed polypeptide chains from the ribosome. In addition to its main function, MRF1 participates in maintaining mitochondrial genome stability. The aim of this study was to investigate the capacity of human homologs, hMTRF1, hMTRF1A, and mitoribosome rescue factors hMTRFR and hMRPL58, to compensate for the absence of the yeast mitochondrial translation termination factor MRF1 in cells. The results obtained suggest that human orthologs of MRF1, such as hMTRF1 and hMTRF1A, can contribute to maintaining the integrity of yeast mitochondrial genome. However, they do not fully make up for the absence of MRF1, as they do not restore normal respiration of the mutant yeast strains.