Mitochondrial ribosome-associated quality control

Mitochondrial ribosome-associated quality control Translation can stall due to lack of tRNAs or due to defects in mRNAs and tRNAs (reviewed in Yip and Shao 2021, Nadler et al. 2022). A stalled mitochondrial 55S ribosome is bound to an mRNA, a tRNA at the exit site (E site), a peptidyl-tRNA at the P site, and a nascent polypeptide covalently attached to a nascent polypeptide covalently attached to the P-site tRNA (that is, a peptidyl-tRNA) (Desai et al. 2020).
In the case of a defective tRNA, dissociation of the complex is initiated by the separation of the 39S and 28S subunits of the stalled 55S ribosome (Desai et al 2020). The MALSU1:MIEF1:NDUFAB1 complex, which normally binds the 39S subunit prior to subunit association during translation initiation, also plays a role in either initiating or maintaining separation of the subunits of the stalled ribosome, as the complex is observed to be associated with the dissociated 39S subunit of a stalled ribosome (Desai et al. 2020). The E-site tRNA, the peptidyl-tRNA, and the nascent polypeptide remain bound to the 39S subunit (Desai et al. 2020).
Subsequent to dissociation of the 39S and 28S subunits, the MTRFR:MTRES1 complex binds the 39S:tRNA:peptidyl-tRNA:polypeptide complex, probably resulting in the ejection of the E-site tRNA (Desai et al. 2020). MTRFR binds the empty A site of the ribosome and MTRES1 binds the anticodon stem-loop of the peptidyl-tRNA (Desai et al. 2020). The MTRFR subunit of the MTRFR:MTRES1 complex is thought to hydrolyze the nascent polypeptide from the peptidyl-tRNA, regenerating the tRNA. MTRFR then ejects the nascent polypeptide and MTRES1 ejects the P-site tRNA.
In the case of a mRNA lacking a stop codon (non-stop mRNA), the ribosome translates to the 3' end of the mRNA. Without a stop codon, neither of the normal mitochondrial translation termination factors, MTRF1L (MTRF1A) or MTRF1, are recruited to the A site of the ribosome to release the nascent polypeptide from the peptidyl-tRNA. Instead, the empty A site and empty mRNA channel are recognized by ICT1 (MRPL58) (Feaga et al. 2016, Kummer et al. 2021) which extends its elongated C-terminal region into the mRNA channel (Kummer et al. 2021). ICT1 then hydrolyzes the peptidyl-tRNA bond to release the nascent polypeptide and regenerate the tRNA (Richter et al. 2010, Feaga et al. 2016). The ribosome is then recycled to yield separate 39S and 28S subunits by an uncharacterized mechanism.