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Role of the AAA protease Yme1 in folding of proteins in the intermembrane space of mitochondria
The vast majority of mitochondrial proteins are synthesized in the cytosol and transported into the organelle in a largely, if not completely, unfolded state. The proper function of mitochondria thus depends on folding of several hundreds of proteins in the various subcompartments of the organelle....
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The American Society for Cell Biology
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3496608/ https://www.ncbi.nlm.nih.gov/pubmed/22993211 http://dx.doi.org/10.1091/mbc.E12-05-0420 |
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author | Schreiner, Bernadette Westerburg, Heike Forné, Ignasi Imhof, Axel Neupert, Walter Mokranjac, Dejana |
author_facet | Schreiner, Bernadette Westerburg, Heike Forné, Ignasi Imhof, Axel Neupert, Walter Mokranjac, Dejana |
author_sort | Schreiner, Bernadette |
collection | PubMed |
description | The vast majority of mitochondrial proteins are synthesized in the cytosol and transported into the organelle in a largely, if not completely, unfolded state. The proper function of mitochondria thus depends on folding of several hundreds of proteins in the various subcompartments of the organelle. Whereas folding of proteins in the mitochondrial matrix is supported by members of several chaperone families, very little is known about folding of proteins in the intermembrane space (IMS). We targeted dihydrofolate reductase (DHFR) as a model substrate to the IMS of yeast mitochondria and analyzed its folding. DHFR can fold in this compartment, and its aggregation upon heat shock can be prevented in an ATP-dependent manner. Yme1, an AAA (ATPases associated with diverse cellular activities) protease of the IMS, prevented aggregation of DHFR. Analysis of protein aggregates in mitochondria lacking Yme1 revealed the presence of a number of proteins involved in the establishment of mitochondrial ultrastructure, lipid metabolism, protein import, and respiratory growth. These findings explain the pleiotropic effects of deletion of YME1 and suggest an important role for Yme1 as a folding assistant, in addition to its proteolytic function, in the protein homeostasis of mitochondria |
format | Online Article Text |
id | pubmed-3496608 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | The American Society for Cell Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-34966082013-01-30 Role of the AAA protease Yme1 in folding of proteins in the intermembrane space of mitochondria Schreiner, Bernadette Westerburg, Heike Forné, Ignasi Imhof, Axel Neupert, Walter Mokranjac, Dejana Mol Biol Cell Articles The vast majority of mitochondrial proteins are synthesized in the cytosol and transported into the organelle in a largely, if not completely, unfolded state. The proper function of mitochondria thus depends on folding of several hundreds of proteins in the various subcompartments of the organelle. Whereas folding of proteins in the mitochondrial matrix is supported by members of several chaperone families, very little is known about folding of proteins in the intermembrane space (IMS). We targeted dihydrofolate reductase (DHFR) as a model substrate to the IMS of yeast mitochondria and analyzed its folding. DHFR can fold in this compartment, and its aggregation upon heat shock can be prevented in an ATP-dependent manner. Yme1, an AAA (ATPases associated with diverse cellular activities) protease of the IMS, prevented aggregation of DHFR. Analysis of protein aggregates in mitochondria lacking Yme1 revealed the presence of a number of proteins involved in the establishment of mitochondrial ultrastructure, lipid metabolism, protein import, and respiratory growth. These findings explain the pleiotropic effects of deletion of YME1 and suggest an important role for Yme1 as a folding assistant, in addition to its proteolytic function, in the protein homeostasis of mitochondria The American Society for Cell Biology 2012-11-15 /pmc/articles/PMC3496608/ /pubmed/22993211 http://dx.doi.org/10.1091/mbc.E12-05-0420 Text en © 2012 Schreiner 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 BD; are registered trademarks of The American Society of Cell Biology. |
spellingShingle | Articles Schreiner, Bernadette Westerburg, Heike Forné, Ignasi Imhof, Axel Neupert, Walter Mokranjac, Dejana Role of the AAA protease Yme1 in folding of proteins in the intermembrane space of mitochondria |
title | Role of the AAA protease Yme1 in folding of proteins in the intermembrane space of mitochondria |
title_full | Role of the AAA protease Yme1 in folding of proteins in the intermembrane space of mitochondria |
title_fullStr | Role of the AAA protease Yme1 in folding of proteins in the intermembrane space of mitochondria |
title_full_unstemmed | Role of the AAA protease Yme1 in folding of proteins in the intermembrane space of mitochondria |
title_short | Role of the AAA protease Yme1 in folding of proteins in the intermembrane space of mitochondria |
title_sort | role of the aaa protease yme1 in folding of proteins in the intermembrane space of mitochondria |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3496608/ https://www.ncbi.nlm.nih.gov/pubmed/22993211 http://dx.doi.org/10.1091/mbc.E12-05-0420 |
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