Cargando…
Mitochondrial enzymes are protected from stress-induced aggregation by mitochondrial chaperones and the Pim1/LON protease
Proteins in a natural environment are constantly challenged by stress conditions, causing their destabilization, unfolding, and, ultimately, aggregation. Protein aggregation has been associated with a wide variety of pathological conditions, especially neurodegenerative disorders, stressing the impo...
Autores principales: | , , , , |
---|---|
Formato: | Texto |
Lenguaje: | English |
Publicado: |
The American Society for Cell Biology
2011
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3046053/ https://www.ncbi.nlm.nih.gov/pubmed/21209324 http://dx.doi.org/10.1091/mbc.E10-08-0718 |
_version_ | 1782198910579638272 |
---|---|
author | Bender, Tom Lewrenz, Ilka Franken, Sebastian Baitzel, Catherina Voos, Wolfgang |
author_facet | Bender, Tom Lewrenz, Ilka Franken, Sebastian Baitzel, Catherina Voos, Wolfgang |
author_sort | Bender, Tom |
collection | PubMed |
description | Proteins in a natural environment are constantly challenged by stress conditions, causing their destabilization, unfolding, and, ultimately, aggregation. Protein aggregation has been associated with a wide variety of pathological conditions, especially neurodegenerative disorders, stressing the importance of adequate cellular protein quality control measures to counteract aggregate formation. To secure protein homeostasis, mitochondria contain an elaborate protein quality control system, consisting of chaperones and ATP-dependent proteases. To determine the effects of protein aggregation on the functional integrity of mitochondria, we set out to identify aggregation-prone endogenous mitochondrial proteins. We could show that major metabolic pathways in mitochondria were affected by the aggregation of key enzyme components, which were largely inactivated after heat stress. Furthermore, treatment with elevated levels of reactive oxygen species strongly influenced the aggregation behavior, in particular in combination with elevated temperatures. Using specific chaperone mutant strains, we showed a protective effect of the mitochondrial Hsp70 and Hsp60 chaperone systems. Moreover, accumulation of aggregated polypeptides was strongly decreased by the AAA-protease Pim1/LON. We therefore propose that the proteolytic breakdown of aggregation-prone polypeptides represents a major protective strategy to prevent the in vivo formation of aggregates in mitochondria. |
format | Text |
id | pubmed-3046053 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | The American Society for Cell Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-30460532011-05-16 Mitochondrial enzymes are protected from stress-induced aggregation by mitochondrial chaperones and the Pim1/LON protease Bender, Tom Lewrenz, Ilka Franken, Sebastian Baitzel, Catherina Voos, Wolfgang Mol Biol Cell Articles Proteins in a natural environment are constantly challenged by stress conditions, causing their destabilization, unfolding, and, ultimately, aggregation. Protein aggregation has been associated with a wide variety of pathological conditions, especially neurodegenerative disorders, stressing the importance of adequate cellular protein quality control measures to counteract aggregate formation. To secure protein homeostasis, mitochondria contain an elaborate protein quality control system, consisting of chaperones and ATP-dependent proteases. To determine the effects of protein aggregation on the functional integrity of mitochondria, we set out to identify aggregation-prone endogenous mitochondrial proteins. We could show that major metabolic pathways in mitochondria were affected by the aggregation of key enzyme components, which were largely inactivated after heat stress. Furthermore, treatment with elevated levels of reactive oxygen species strongly influenced the aggregation behavior, in particular in combination with elevated temperatures. Using specific chaperone mutant strains, we showed a protective effect of the mitochondrial Hsp70 and Hsp60 chaperone systems. Moreover, accumulation of aggregated polypeptides was strongly decreased by the AAA-protease Pim1/LON. We therefore propose that the proteolytic breakdown of aggregation-prone polypeptides represents a major protective strategy to prevent the in vivo formation of aggregates in mitochondria. The American Society for Cell Biology 2011-03-01 /pmc/articles/PMC3046053/ /pubmed/21209324 http://dx.doi.org/10.1091/mbc.E10-08-0718 Text en © 2011 Bender et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). “ASCB®,“ “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society of Cell Biology. |
spellingShingle | Articles Bender, Tom Lewrenz, Ilka Franken, Sebastian Baitzel, Catherina Voos, Wolfgang Mitochondrial enzymes are protected from stress-induced aggregation by mitochondrial chaperones and the Pim1/LON protease |
title | Mitochondrial enzymes are protected from stress-induced aggregation by mitochondrial chaperones and the Pim1/LON protease |
title_full | Mitochondrial enzymes are protected from stress-induced aggregation by mitochondrial chaperones and the Pim1/LON protease |
title_fullStr | Mitochondrial enzymes are protected from stress-induced aggregation by mitochondrial chaperones and the Pim1/LON protease |
title_full_unstemmed | Mitochondrial enzymes are protected from stress-induced aggregation by mitochondrial chaperones and the Pim1/LON protease |
title_short | Mitochondrial enzymes are protected from stress-induced aggregation by mitochondrial chaperones and the Pim1/LON protease |
title_sort | mitochondrial enzymes are protected from stress-induced aggregation by mitochondrial chaperones and the pim1/lon protease |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3046053/ https://www.ncbi.nlm.nih.gov/pubmed/21209324 http://dx.doi.org/10.1091/mbc.E10-08-0718 |
work_keys_str_mv | AT bendertom mitochondrialenzymesareprotectedfromstressinducedaggregationbymitochondrialchaperonesandthepim1lonprotease AT lewrenzilka mitochondrialenzymesareprotectedfromstressinducedaggregationbymitochondrialchaperonesandthepim1lonprotease AT frankensebastian mitochondrialenzymesareprotectedfromstressinducedaggregationbymitochondrialchaperonesandthepim1lonprotease AT baitzelcatherina mitochondrialenzymesareprotectedfromstressinducedaggregationbymitochondrialchaperonesandthepim1lonprotease AT vooswolfgang mitochondrialenzymesareprotectedfromstressinducedaggregationbymitochondrialchaperonesandthepim1lonprotease |