Reference - PMID:41118763 - Delayed protein translocation protects mitochondria against toxic CAT-tailed proteins.
Reference summary
- PubMed ID
- PMID:41118763
- Title
- Delayed protein translocation protects mitochondria against toxic CAT-tailed proteins.
- Authors
- Bertram N, Izawa T, Thoma F, Schwenkert S, Duvezin-Caubet S, Park SH, Wagener N, Devin A, Osman C, Neupert W, Mokranjac D
- Citation
- Mol Cell 2025 Nov 06;85(21):4082-4092.e7
- Publication year
- 2025
- Abstract
- Ribosome-associated protein quality control (RQC) protects cells against the toxic effects of faulty polypeptides produced by stalled ribosomes. However, mitochondria are vulnerable to C-terminal alanyl and threonyl (CAT)-tailed proteins that are generated in this process, and faulty nuclear-encoded mitochondrial proteins are handled by the recently discovered mitoRQC. Here, we performed a genome-wide screen in yeast to identify additional proteins involved in mitoRQC. We found that peptidyl-tRNA hydrolase 2 (Pth2), present in the mitochondrial outer membrane, influences aggregation of CAT-tailed proteins without majorly affecting the CAT-tailing process itself. Peptidyl-tRNA hydrolase activity is essential during this process, yet the activity of Pth2 can be substituted by another peptidyl-tRNA hydrolase upon proper localization. Our data suggest that Pth2 acts by modulating protein translocation and that the mitochondrial proteostasis network is relieved through increased access of CAT-tailed proteins to cytosolic chaperones. Other hits obtained in the screen show that, in general, delayed protein translocation protects mitochondria against toxic CAT-tailed proteins.
