Msp1 Clears Mistargeted Proteins by Facilitating Their Transfer from Mitochondria to the ER
| Autor: | Masatoshi Esaki, Shunsuke Matsumoto, Yasushi Tamura, Kunio Nakatsukasa, Toshiya Endo, Chika Kakuta |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Proteasome Endopeptidase Complex
Saccharomyces cerevisiae Proteins Ubiquitin-Protein Ligases Saccharomyces cerevisiae Biology Mitochondrion Endoplasmic Reticulum 03 medical and health sciences 0302 clinical medicine Ubiquitin ER membrane Valosin Containing Protein parasitic diseases Molecular Biology 030304 developmental biology Adenosine Triphosphatases 0303 health sciences Endoplasmic reticulum Ubiquitination Cell Biology Cell biology Mitochondria Cytosol Protein Transport Mitochondrial Membranes Proteolysis biology.protein Bacterial outer membrane Protein quality 030217 neurology & neurosurgery |
| Zdroj: | Molecular cell. 76(1) |
| ISSN: | 1097-4164 |
| Popis: | Normal mitochondrial functions rely on optimized composition of their resident proteins, and proteins mistargeted to mitochondria need to be efficiently removed. Msp1, an AAA-ATPase in the mitochondrial outer membrane (OM), facilitates degradation of tail-anchored (TA) proteins mistargeted to the OM, yet how Msp1 cooperates with other factors to conduct this process was unclear. Here, we show that Msp1 recognizes substrate TA proteins and facilitates their transfer to the endoplasmic reticulum (ER). Doa10 in the ER membrane then ubiquitinates them with Ubc6 and Ubc7. Ubiquitinated substrates are extracted from the ER membrane by another AAA-ATPase in the cytosol, Cdc48, with Ufd1 and Npl4 for proteasomal degradation in the cytosol. Thus, Msp1 functions as an extractase that mediates clearance of mistargeted TA proteins by facilitating their transfer to the ER for protein quality control. |
| Databáze: | OpenAIRE |
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