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Parkin-mediated ubiquitination contributes to the constitutive turnover of mitochondrial fission factor (Mff)

The mitochondrial outer membrane protein Mitochondrial Fission Factor (Mff) plays a key role in both physiological and pathological fission. It is well established that at stressed or functionally impaired mitochondria, PINK1 recruits the ubiquitin ligase Parkin which ubiquitinates Mff and other mit...

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Detalles Bibliográficos
Autores principales: Lee, Laura, Seager, Richard, Nakamura, Yasuko, Wilkinson, Kevin A., Henley, Jeremy M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6528996/
https://www.ncbi.nlm.nih.gov/pubmed/31112535
http://dx.doi.org/10.1371/journal.pone.0213116
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author Lee, Laura
Seager, Richard
Nakamura, Yasuko
Wilkinson, Kevin A.
Henley, Jeremy M.
author_facet Lee, Laura
Seager, Richard
Nakamura, Yasuko
Wilkinson, Kevin A.
Henley, Jeremy M.
author_sort Lee, Laura
collection PubMed
description The mitochondrial outer membrane protein Mitochondrial Fission Factor (Mff) plays a key role in both physiological and pathological fission. It is well established that at stressed or functionally impaired mitochondria, PINK1 recruits the ubiquitin ligase Parkin which ubiquitinates Mff and other mitochondrial outer membrane proteins to facilitate the removal of defective mitochondria and maintain the integrity of the mitochondrial network. Here we show that, in addition to this clearance pathway, Parkin also ubiquitinates Mff in a PINK1-dependent manner under non-stressed conditions to regulate constitutive Mff turnover. We further show that removing Parkin via shRNA-mediated knockdown does not completely prevent Mff ubiquitination under these conditions, indicating that at least one other ubiquitin ligase contributes to Mff proteostasis. These data suggest that that Parkin plays a role in physiological maintenance of mitochondrial membrane protein composition in unstressed cells through constitutive low-level activation.
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spelling pubmed-65289962019-05-31 Parkin-mediated ubiquitination contributes to the constitutive turnover of mitochondrial fission factor (Mff) Lee, Laura Seager, Richard Nakamura, Yasuko Wilkinson, Kevin A. Henley, Jeremy M. PLoS One Research Article The mitochondrial outer membrane protein Mitochondrial Fission Factor (Mff) plays a key role in both physiological and pathological fission. It is well established that at stressed or functionally impaired mitochondria, PINK1 recruits the ubiquitin ligase Parkin which ubiquitinates Mff and other mitochondrial outer membrane proteins to facilitate the removal of defective mitochondria and maintain the integrity of the mitochondrial network. Here we show that, in addition to this clearance pathway, Parkin also ubiquitinates Mff in a PINK1-dependent manner under non-stressed conditions to regulate constitutive Mff turnover. We further show that removing Parkin via shRNA-mediated knockdown does not completely prevent Mff ubiquitination under these conditions, indicating that at least one other ubiquitin ligase contributes to Mff proteostasis. These data suggest that that Parkin plays a role in physiological maintenance of mitochondrial membrane protein composition in unstressed cells through constitutive low-level activation. Public Library of Science 2019-05-21 /pmc/articles/PMC6528996/ /pubmed/31112535 http://dx.doi.org/10.1371/journal.pone.0213116 Text en © 2019 Lee et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Lee, Laura
Seager, Richard
Nakamura, Yasuko
Wilkinson, Kevin A.
Henley, Jeremy M.
Parkin-mediated ubiquitination contributes to the constitutive turnover of mitochondrial fission factor (Mff)
title Parkin-mediated ubiquitination contributes to the constitutive turnover of mitochondrial fission factor (Mff)
title_full Parkin-mediated ubiquitination contributes to the constitutive turnover of mitochondrial fission factor (Mff)
title_fullStr Parkin-mediated ubiquitination contributes to the constitutive turnover of mitochondrial fission factor (Mff)
title_full_unstemmed Parkin-mediated ubiquitination contributes to the constitutive turnover of mitochondrial fission factor (Mff)
title_short Parkin-mediated ubiquitination contributes to the constitutive turnover of mitochondrial fission factor (Mff)
title_sort parkin-mediated ubiquitination contributes to the constitutive turnover of mitochondrial fission factor (mff)
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6528996/
https://www.ncbi.nlm.nih.gov/pubmed/31112535
http://dx.doi.org/10.1371/journal.pone.0213116
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