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Selective sorting and destruction of mitochondrial membrane proteins in aged yeast

Mitochondrial dysfunction is a hallmark of aging, and underlies the development of many diseases. Cells maintain mitochondrial homeostasis through a number of pathways that remodel the mitochondrial proteome or alter mitochondrial content during times of stress or metabolic adaptation. Here, using y...

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Autores principales: Hughes, Adam L, Hughes, Casey E, Henderson, Kiersten A, Yazvenko, Nina, Gottschling, Daniel E
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4889329/
https://www.ncbi.nlm.nih.gov/pubmed/27097106
http://dx.doi.org/10.7554/eLife.13943
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author Hughes, Adam L
Hughes, Casey E
Henderson, Kiersten A
Yazvenko, Nina
Gottschling, Daniel E
author_facet Hughes, Adam L
Hughes, Casey E
Henderson, Kiersten A
Yazvenko, Nina
Gottschling, Daniel E
author_sort Hughes, Adam L
collection PubMed
description Mitochondrial dysfunction is a hallmark of aging, and underlies the development of many diseases. Cells maintain mitochondrial homeostasis through a number of pathways that remodel the mitochondrial proteome or alter mitochondrial content during times of stress or metabolic adaptation. Here, using yeast as a model system, we identify a new mitochondrial degradation system that remodels the mitochondrial proteome of aged cells. Unlike many common mitochondrial degradation pathways, this system selectively removes a subset of membrane proteins from the mitochondrial inner and outer membranes, while leaving the remainder of the organelle intact. Selective removal of preexisting proteins is achieved by sorting into a mitochondrial-derived compartment, or MDC, followed by release through mitochondrial fission and elimination by autophagy. Formation of MDCs requires the import receptors Tom70/71, and failure to form these structures exacerbates preexisting mitochondrial dysfunction, suggesting that the MDC pathway provides protection to mitochondria in times of stress. DOI: http://dx.doi.org/10.7554/eLife.13943.001
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spelling pubmed-48893292016-06-02 Selective sorting and destruction of mitochondrial membrane proteins in aged yeast Hughes, Adam L Hughes, Casey E Henderson, Kiersten A Yazvenko, Nina Gottschling, Daniel E eLife Cell Biology Mitochondrial dysfunction is a hallmark of aging, and underlies the development of many diseases. Cells maintain mitochondrial homeostasis through a number of pathways that remodel the mitochondrial proteome or alter mitochondrial content during times of stress or metabolic adaptation. Here, using yeast as a model system, we identify a new mitochondrial degradation system that remodels the mitochondrial proteome of aged cells. Unlike many common mitochondrial degradation pathways, this system selectively removes a subset of membrane proteins from the mitochondrial inner and outer membranes, while leaving the remainder of the organelle intact. Selective removal of preexisting proteins is achieved by sorting into a mitochondrial-derived compartment, or MDC, followed by release through mitochondrial fission and elimination by autophagy. Formation of MDCs requires the import receptors Tom70/71, and failure to form these structures exacerbates preexisting mitochondrial dysfunction, suggesting that the MDC pathway provides protection to mitochondria in times of stress. DOI: http://dx.doi.org/10.7554/eLife.13943.001 eLife Sciences Publications, Ltd 2016-04-20 /pmc/articles/PMC4889329/ /pubmed/27097106 http://dx.doi.org/10.7554/eLife.13943 Text en © 2016, Hughes et al http://creativecommons.org/licenses/by/4.0/ This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Cell Biology
Hughes, Adam L
Hughes, Casey E
Henderson, Kiersten A
Yazvenko, Nina
Gottschling, Daniel E
Selective sorting and destruction of mitochondrial membrane proteins in aged yeast
title Selective sorting and destruction of mitochondrial membrane proteins in aged yeast
title_full Selective sorting and destruction of mitochondrial membrane proteins in aged yeast
title_fullStr Selective sorting and destruction of mitochondrial membrane proteins in aged yeast
title_full_unstemmed Selective sorting and destruction of mitochondrial membrane proteins in aged yeast
title_short Selective sorting and destruction of mitochondrial membrane proteins in aged yeast
title_sort selective sorting and destruction of mitochondrial membrane proteins in aged yeast
topic Cell Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4889329/
https://www.ncbi.nlm.nih.gov/pubmed/27097106
http://dx.doi.org/10.7554/eLife.13943
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