The AAA protein Msp1 mediates clearance of excess tail-anchored proteins from the peroxisomal membrane

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Abstract

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.

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The following data sets were generated

(2017) Data from: The AAA protein Msp1 mediates clearance of excess tail-anchored proteins from the peroxisomal membrane
Available at Dryad Digital Repository under a CC0 Public Domain Dedication.

http://dx.doi.org/10.5061/dryad.pc4d6

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Author details

Nicholas R Weir

Department of Molecular and Cellular Biology, Harvard University, Cambridge, United States

Competing interests
The authors declare that no competing interests exist.
Roarke A Kamber

Department of Molecular and Cellular Biology, Harvard University, Cambridge, United States

Competing interests
The authors declare that no competing interests exist.
James S Martenson

Department of Molecular and Cellular Biology, Harvard University, Cambridge, United States

Competing interests
The authors declare that no competing interests exist.
Vladimir Denic

Department of Molecular and Cellular Biology, Harvard University, Cambridge, United States

For correspondence
vdenic@mcb.harvard.edu

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0002-1982-7281

Funding

National Institutes of Health

Vladimir Denic

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

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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.