All mechanisms of protein synthesis can be considered in four stages: initiation, elongation, termination, and ribosome recycling. Remarkable progress has been made in understanding how these processes are mediated in the cytosol of many species; however, details of organellar protein synthesis remain sketchy. This is an important omission, as defects in human mitochondrial translation are known to cause disease and may contribute to the aging process itself. In this minireview, we focus on the recent advances that have been made in understanding how one of these processes, translation termination, occurs in the human mitochondrion.The synthesis of proteins is a fundamental mechanism of life. It is clearly essential that the process of mRNA translation, from which proteins are generated, is accurate and well controlled. Translation consists of four stages. The first is initiation, in which a repertoire of initiation factors coordinates the association of mRNA with the ribosomal subunits, recognition of the start codon, and its alignment with an fMet-tRNA Met in the ribosomal P-site. The second stage is elongation, which is facilitated by the action of elongation factors. These act in concert, causing the mRNA to move through the ribosome in steps corresponding to three nucleotides commonly referred to as a codon (1). This stepwise progression allows each codon to be decoded by the cognate aminoacylated tRNA, with the consequent addition of the corresponding amino acid to the nascent polypeptide (2). The third stage is termination, which occurs when a stop codon arrives in the ribosomal A-site and is recognized by a trans-acting protein termed a translation release (RF) 2 or termination factor. This acts in a ribosome-dependent manner, resulting in the nascent polypeptide being separated from the P-site tRNA, allowing the newly synthesized protein to be released from the ribosome. The final stage is that of ribosome recycling, in which the large (LSU) and small (SSU) ribosomal subunits are separated, and the mRNA is released so that the components can be used in a fresh cycle of translation.Extensive research on these individual steps has shown that, across the three domains of life, there are differences in both the cis-and trans-acting factors involved in carrying out these processes, resulting in mechanistic variations. Moreover, investigations into intraorganellar protein synthesis suggest that there are further subtleties to this process, with differences even between organelles from different organisms. To illustrate how the systems can differ as well as retain similarities, this minireview will concentrate on a single step in this process, namely translation termination, and focus on how mitochondria have organized their machinery to accomplish this process.
TerminationTermination of translation occurs when a stop codon becomes positioned in the ribosomal A-site and is decoded by a protein moiety. This trans-acting factor (an RF) acts in an analogous fashion to the tRNAs, as it shows sequence-specific reco...