Cytosolic Protein Vms1 Links Ribosome Quality Control to Mitochondrial and Cellular Homeostasis
Eukaryotic cells have evolved extensive protein quality-control mechanisms to remove faulty translation products. Here, we show that yeast cells continually produce faulty mitochondrial polypeptides that stall on the ribosome during translation but are imported into the mitochondria. The cytosolic p...
Saved in:
Published in | Cell Vol. 171; no. 4; pp. 890 - 903.e18 |
---|---|
Main Authors | , , , , |
Format | Journal Article |
Language | English |
Published |
United States
Elsevier Inc
02.11.2017
|
Subjects | |
Online Access | Get full text |
Cover
Loading…
Summary: | Eukaryotic cells have evolved extensive protein quality-control mechanisms to remove faulty translation products. Here, we show that yeast cells continually produce faulty mitochondrial polypeptides that stall on the ribosome during translation but are imported into the mitochondria. The cytosolic protein Vms1, together with the E3 ligase Ltn1, protects against the mitochondrial toxicity of these proteins and maintains cell viability under respiratory conditions. In the absence of these factors, stalled polypeptides aggregate after import and sequester critical mitochondrial chaperone and translation machinery. Aggregation depends on C-terminal alanyl/threonyl sequences (CAT-tails) that are attached to stalled polypeptides on 60S ribosomes by Rqc2. Vms1 binds to 60S ribosomes at the mitochondrial surface and antagonizes Rqc2, thereby facilitating import, impeding aggregation, and directing aberrant polypeptides to intra-mitochondrial quality control. Vms1 is a key component of a rescue pathway for ribosome-stalled mitochondrial polypeptides that are inaccessible to ubiquitylation due to coupling of translation and translocation.
[Display omitted]
•Cytosolic Vms1 protects cells from mitochondrial toxicity of ribosome-stalled proteins•Stalled polypeptides aggregate inside mitochondria, dependent on CAT-tail sequences•Vms1 antagonizes CAT tailing by Rqc2, thereby avoiding aggregate formation•Vms1 is a key component of a ribosome quality-control pathway termed mitoRQC
A quality-control pathway comprising the cytosolic protein Vms1 protects mitochondria from the toxic effects of ribosome-stalled polypeptides. |
---|---|
Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0092-8674 1097-4172 |
DOI: | 10.1016/j.cell.2017.10.002 |