Crosstalk between cellular compartments protects against proteotoxicity and extends lifespan
In cells living under optimal conditions, protein folding defects are usually prevented by the action of chaperones. Here, we investigate the cell-wide consequences of loss of chaperone function in cytosol, mitochondria or the endoplasmic reticulum (ER) in budding yeast. We find that the decline in...
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| Format: | Online |
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Nature Publishing Group
2016
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| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4921836/ |
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pubmed-49218362016-06-28 Crosstalk between cellular compartments protects against proteotoxicity and extends lifespan Perić, Matea Dib, Peter Bou Dennerlein, Sven Musa, Marina Rudan, Marina Lovrić, Anita Nikolić, Andrea Šarić, Ana Sobočanec, Sandra Mačak, Željka Raimundo, Nuno Kriško, Anita Article In cells living under optimal conditions, protein folding defects are usually prevented by the action of chaperones. Here, we investigate the cell-wide consequences of loss of chaperone function in cytosol, mitochondria or the endoplasmic reticulum (ER) in budding yeast. We find that the decline in chaperone activity in each compartment results in loss of respiration, demonstrating the dependence of mitochondrial activity on cell-wide proteostasis. Furthermore, each chaperone deficiency triggers a response, presumably via the communication among the folding environments of distinct cellular compartments, termed here the cross-organelle stress response (CORE). The proposed CORE pathway encompasses activation of protein conformational maintenance machineries, antioxidant enzymes, and metabolic changes simultaneously in the cytosol, mitochondria, and the ER. CORE induction extends replicative and chronological lifespan in budding yeast, highlighting its protective role against moderate proteotoxicity and its consequences such as the decline in respiration. Our findings accentuate that organelles do not function in isolation, but are integrated in a functional crosstalk, while also highlighting the importance of organelle communication in aging and age-related diseases. Nature Publishing Group 2016-06-27 /pmc/articles/PMC4921836/ /pubmed/27346163 http://dx.doi.org/10.1038/srep28751 Text en Copyright © 2016, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
| repository_type |
Open Access Journal |
| institution_category |
Foreign Institution |
| institution |
US National Center for Biotechnology Information |
| building |
NCBI PubMed |
| collection |
Online Access |
| language |
English |
| format |
Online |
| author |
Perić, Matea Dib, Peter Bou Dennerlein, Sven Musa, Marina Rudan, Marina Lovrić, Anita Nikolić, Andrea Šarić, Ana Sobočanec, Sandra Mačak, Željka Raimundo, Nuno Kriško, Anita |
| spellingShingle |
Perić, Matea Dib, Peter Bou Dennerlein, Sven Musa, Marina Rudan, Marina Lovrić, Anita Nikolić, Andrea Šarić, Ana Sobočanec, Sandra Mačak, Željka Raimundo, Nuno Kriško, Anita Crosstalk between cellular compartments protects against proteotoxicity and extends lifespan |
| author_facet |
Perić, Matea Dib, Peter Bou Dennerlein, Sven Musa, Marina Rudan, Marina Lovrić, Anita Nikolić, Andrea Šarić, Ana Sobočanec, Sandra Mačak, Željka Raimundo, Nuno Kriško, Anita |
| author_sort |
Perić, Matea |
| title |
Crosstalk between cellular compartments protects against proteotoxicity and extends lifespan |
| title_short |
Crosstalk between cellular compartments protects against proteotoxicity and extends lifespan |
| title_full |
Crosstalk between cellular compartments protects against proteotoxicity and extends lifespan |
| title_fullStr |
Crosstalk between cellular compartments protects against proteotoxicity and extends lifespan |
| title_full_unstemmed |
Crosstalk between cellular compartments protects against proteotoxicity and extends lifespan |
| title_sort |
crosstalk between cellular compartments protects against proteotoxicity and extends lifespan |
| description |
In cells living under optimal conditions, protein folding defects are usually prevented by the action of chaperones. Here, we investigate the cell-wide consequences of loss of chaperone function in cytosol, mitochondria or the endoplasmic reticulum (ER) in budding yeast. We find that the decline in chaperone activity in each compartment results in loss of respiration, demonstrating the dependence of mitochondrial activity on cell-wide proteostasis. Furthermore, each chaperone deficiency triggers a response, presumably via the communication among the folding environments of distinct cellular compartments, termed here the cross-organelle stress response (CORE). The proposed CORE pathway encompasses activation of protein conformational maintenance machineries, antioxidant enzymes, and metabolic changes simultaneously in the cytosol, mitochondria, and the ER. CORE induction extends replicative and chronological lifespan in budding yeast, highlighting its protective role against moderate proteotoxicity and its consequences such as the decline in respiration. Our findings accentuate that organelles do not function in isolation, but are integrated in a functional crosstalk, while also highlighting the importance of organelle communication in aging and age-related diseases. |
| publisher |
Nature Publishing Group |
| publishDate |
2016 |
| url |
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4921836/ |
| _version_ |
1613599908734959616 |