The AAA protein Msp1 mediates clearance of excess tail-anchored proteins from the peroxisomal membrane
Msp1 is a conserved AAA ATPase in budding yeast localized to mitochondria where it prevents accumulation of mistargeted tail-anchored (TA) proteins, including the peroxisomal TA protein Pex15. Msp1 also resides on peroxisomes but it remains unknown how native TA proteins on mitochondria and peroxiso...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
| Published: |
eLife Sciences Publications Ltd
2017-09-01
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| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/28507 |
| _version_ | 1811200741477449728 |
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| author | Nicholas R Weir Roarke A Kamber James S Martenson Vladimir Denic |
| author_facet | Nicholas R Weir Roarke A Kamber James S Martenson Vladimir Denic |
| author_sort | Nicholas R Weir |
| collection | DOAJ |
| description | Msp1 is a conserved AAA ATPase in budding yeast localized to mitochondria where it prevents accumulation of mistargeted tail-anchored (TA) proteins, including the peroxisomal TA protein Pex15. Msp1 also resides on peroxisomes but it remains unknown how native TA proteins on mitochondria and peroxisomes evade Msp1 surveillance. We used live-cell quantitative cell microscopy tools and drug-inducible gene expression to dissect Msp1 function. We found that a small fraction of peroxisomal Pex15, exaggerated by overexpression, is turned over by Msp1. Kinetic measurements guided by theoretical modeling revealed that Pex15 molecules at mitochondria display age-independent Msp1 sensitivity. By contrast, Pex15 molecules at peroxisomes are rapidly converted from an initial Msp1-sensitive to an Msp1-resistant state. Lastly, we show that Pex15 interacts with the peroxisomal membrane protein Pex3, which shields Pex15 from Msp1-dependent turnover. In sum, our work argues that Msp1 selects its substrates on the basis of their solitary membrane existence. |
| first_indexed | 2024-04-12T02:08:47Z |
| format | Article |
| id | doaj.art-423c5120da494857b5884657a9ad6529 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T02:08:47Z |
| publishDate | 2017-09-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-423c5120da494857b5884657a9ad65292022-12-22T03:52:27ZengeLife Sciences Publications LtdeLife2050-084X2017-09-01610.7554/eLife.28507The AAA protein Msp1 mediates clearance of excess tail-anchored proteins from the peroxisomal membraneNicholas R Weir0https://orcid.org/0000-0002-1797-849XRoarke A Kamber1James S Martenson2Vladimir Denic3https://orcid.org/0000-0002-1982-7281Department of Molecular and Cellular Biology, Harvard University, Cambridge, United StatesDepartment of Molecular and Cellular Biology, Harvard University, Cambridge, United StatesDepartment of Molecular and Cellular Biology, Harvard University, Cambridge, United StatesDepartment of Molecular and Cellular Biology, Harvard University, Cambridge, United StatesMsp1 is a conserved AAA ATPase in budding yeast localized to mitochondria where it prevents accumulation of mistargeted tail-anchored (TA) proteins, including the peroxisomal TA protein Pex15. Msp1 also resides on peroxisomes but it remains unknown how native TA proteins on mitochondria and peroxisomes evade Msp1 surveillance. We used live-cell quantitative cell microscopy tools and drug-inducible gene expression to dissect Msp1 function. We found that a small fraction of peroxisomal Pex15, exaggerated by overexpression, is turned over by Msp1. Kinetic measurements guided by theoretical modeling revealed that Pex15 molecules at mitochondria display age-independent Msp1 sensitivity. By contrast, Pex15 molecules at peroxisomes are rapidly converted from an initial Msp1-sensitive to an Msp1-resistant state. Lastly, we show that Pex15 interacts with the peroxisomal membrane protein Pex3, which shields Pex15 from Msp1-dependent turnover. In sum, our work argues that Msp1 selects its substrates on the basis of their solitary membrane existence.https://elifesciences.org/articles/28507quality controlAAA ATPasetail-anchored proteinmitochondriaperoxisome |
| spellingShingle | Nicholas R Weir Roarke A Kamber James S Martenson Vladimir Denic The AAA protein Msp1 mediates clearance of excess tail-anchored proteins from the peroxisomal membrane eLife quality control AAA ATPase tail-anchored protein mitochondria peroxisome |
| title | The AAA protein Msp1 mediates clearance of excess tail-anchored proteins from the peroxisomal membrane |
| title_full | The AAA protein Msp1 mediates clearance of excess tail-anchored proteins from the peroxisomal membrane |
| title_fullStr | The AAA protein Msp1 mediates clearance of excess tail-anchored proteins from the peroxisomal membrane |
| title_full_unstemmed | The AAA protein Msp1 mediates clearance of excess tail-anchored proteins from the peroxisomal membrane |
| title_short | The AAA protein Msp1 mediates clearance of excess tail-anchored proteins from the peroxisomal membrane |
| title_sort | aaa protein msp1 mediates clearance of excess tail anchored proteins from the peroxisomal membrane |
| topic | quality control AAA ATPase tail-anchored protein mitochondria peroxisome |
| url | https://elifesciences.org/articles/28507 |
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