NOA1, a Novel ClpXP Substrate, Takes an Unexpected Nuclear Detour Prior to Mitochondrial Import
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...
| Main Authors: | , , , , , |
|---|---|
| Other Authors: | |
| Format: | Article |
| Language: | en_US |
| Published: |
Public Library of Science
2014
|
| Online Access: | http://hdl.handle.net/1721.1/89227 https://orcid.org/0000-0002-6621-4461 |
| _version_ | 1826208060372156416 |
|---|---|
| author | Al-Furoukh, Natalie Krüger, Marcus Szibor, Marten Baker, Tania Braun, Thomas Kardon, Julia R. |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Al-Furoukh, Natalie Krüger, Marcus Szibor, Marten Baker, Tania Braun, Thomas Kardon, Julia R. |
| author_sort | Al-Furoukh, Natalie |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T13:59:53Z |
| format | Article |
| id | mit-1721.1/89227 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T13:59:53Z |
| publishDate | 2014 |
| publisher | Public Library of Science |
| record_format | dspace |
| spelling | mit-1721.1/892272022-09-28T17:34:59Z NOA1, a Novel ClpXP Substrate, Takes an Unexpected Nuclear Detour Prior to Mitochondrial Import Al-Furoukh, Natalie Krüger, Marcus Szibor, Marten Baker, Tania Braun, Thomas Kardon, Julia R. Massachusetts Institute of Technology. Department of Biology Kardon, Julia Ruth Baker, Tania 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. Max Planck Society for the Advancement of Science 2014-09-09T15:19:28Z 2014-09-09T15:19:28Z 2014-07 2014-03 Article http://purl.org/eprint/type/JournalArticle 1932-6203 http://hdl.handle.net/1721.1/89227 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. https://orcid.org/0000-0002-6621-4461 en_US http://dx.doi.org/10.1371/journal.pone.0103141 PLoS ONE Creative Commons Attribution http://creativecommons.org/licenses/by/4.0/ application/pdf Public Library of Science Public Library of Science |
| spellingShingle | Al-Furoukh, Natalie Krüger, Marcus Szibor, Marten Baker, Tania Braun, Thomas Kardon, Julia R. NOA1, a Novel ClpXP Substrate, Takes an Unexpected Nuclear Detour Prior to Mitochondrial Import |
| title | NOA1, a Novel ClpXP Substrate, Takes an Unexpected Nuclear Detour Prior to Mitochondrial Import |
| title_full | NOA1, a Novel ClpXP Substrate, Takes an Unexpected Nuclear Detour Prior to Mitochondrial Import |
| title_fullStr | NOA1, a Novel ClpXP Substrate, Takes an Unexpected Nuclear Detour Prior to Mitochondrial Import |
| title_full_unstemmed | NOA1, a Novel ClpXP Substrate, Takes an Unexpected Nuclear Detour Prior to Mitochondrial Import |
| title_short | NOA1, a Novel ClpXP Substrate, Takes an Unexpected Nuclear Detour Prior to Mitochondrial Import |
| title_sort | noa1 a novel clpxp substrate takes an unexpected nuclear detour prior to mitochondrial import |
| url | http://hdl.handle.net/1721.1/89227 https://orcid.org/0000-0002-6621-4461 |
| work_keys_str_mv | AT alfuroukhnatalie noa1anovelclpxpsubstratetakesanunexpectednucleardetourpriortomitochondrialimport AT krugermarcus noa1anovelclpxpsubstratetakesanunexpectednucleardetourpriortomitochondrialimport AT szibormarten noa1anovelclpxpsubstratetakesanunexpectednucleardetourpriortomitochondrialimport AT bakertania noa1anovelclpxpsubstratetakesanunexpectednucleardetourpriortomitochondrialimport AT braunthomas noa1anovelclpxpsubstratetakesanunexpectednucleardetourpriortomitochondrialimport AT kardonjuliar noa1anovelclpxpsubstratetakesanunexpectednucleardetourpriortomitochondrialimport |