NOA1, a Novel ClpXP Substrate, Takes an Unexpected Nuclear Detour Prior to Mitochondrial Import
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Al-Furoukh-2014-NOA1, a Novel ClpXP.pdf
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Author(s)
Al-Furoukh, Natalie
Krüger, Marcus
Szibor, Marten
Baker, Tania
Braun, Thomas
Kardon, Julia R.
Date Issued
July 2014
Journal
PLoS ONE
Publisher
Public Library of Science
Citation
Al-Furoukh, Natalie, Julia R. Kardon, Marcus Krüger, Marten Szibor, Tania A. Baker, and Thomas Braun. “NOA1, a Novel ClpXP Substrate, Takes an Unexpected Nuclear Detour Prior to Mitochondrial Import.” Edited by Vimal Selvaraj. PLoS ONE 9, no. 7 (July 29, 2014): e103141.
Version
Final published version
Abstract
The mitochondrial matrix GTPase NOA1 is a nuclear encoded protein, essential for mitochondrial protein synthesis, oxidative phosphorylation and ATP production. Here, we demonstrate that newly translated NOA1 protein is imported into the nucleus, where it localizes to the nucleolus and interacts with UBF1 before nuclear export and import into mitochondria. Mutation of the nuclear localization signal (NLS) prevented both nuclear and mitochondrial import while deletion of the N-terminal mitochondrial targeting sequence (MTS) or the C-terminal RNA binding domain of NOA1 impaired mitochondrial import. Absence of the MTS resulted in accumulation of NOA1 in the nucleus and increased caspase-dependent apoptosis. We also found that export of NOA1 from the nucleus requires a leptomycin-B sensitive, Crm1-dependent nuclear export signal (NES). Finally, we show that NOA1 is a new substrate of the mitochondrial matrix protease complex ClpXP. Our results uncovered an unexpected, mandatory detour of NOA1 through the nucleolus before uptake into mitochondria. We propose that nucleo-mitochondrial translocation of proteins is more widespread than previously anticipated providing additional means to control protein bioavailability as well as cellular communication between both compartments.
MIT Department
Massachusetts Institute of Technology. Department of Biology
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DOI of Published Version
https://doi.org/10.1371/journal.pone.0103141
