Cooperation of mitochondrial and ER factors in quality control of tail-anchored proteins
- University of Heidelberg, Germany
- Institute of Molecular Biology (IMB), Germany
- Calico Life Sciences LLC, United States
Abstract
Tail-anchored (TA) proteins insert post-translationally into the endoplasmic reticulum (ER), the outer mitochondrial membrane (OMM) and peroxisomes. Whereas the GET pathway controls ER-targeting, no dedicated factors are known for OMM insertion, posing the question of how accuracy is achieved. The mitochondrial AAA-ATPase Msp1 removes mislocalized TA proteins from the OMM, but it is unclear, how Msp1 clients are targeted for degradation. Here we screened for factors involved in degradation of TA proteins mislocalized to mitochondria. We show that the ER-associated degradation (ERAD) E3 ubiquitin ligase Doa10 controls cytoplasmic level of Msp1 clients. Furthermore, we identified the uncharacterized OMM protein Fmp32 and the ectopically expressed subunit of the ER-mitochondria encounter structure (ERMES) complex Gem1 as native clients for Msp1 and Doa10. We propose that productive localization of TA proteins to the OMM is ensured by complex assembly, while orphan subunits are extracted by Msp1 and eventually degraded by Doa10.
Data availability
All data generated or analysed during this study are included in the manuscript and supporting files.
Article and author information
Author details
Funding
Deutsche Forschungsgemeinschaft (SFB1036/2 TP10)
- Anton Khmelinskii
Deutsche Forschungsgemeinschaft (SFB1036/2 TP10)
- Michael Knop
Deutsche Forschungsgemeinschaft (SFB1036/2 TP12)
- Marius K Lemberg
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2019, Dederer et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Cooperation of mitochondrial and ER factors in quality control of tail-anchored proteins
eLife 8:e45506.
https://doi.org/10.7554/eLife.45506
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