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Metabolic regulation of misfolded protein import into mitochondria
Mitochondria are the cellular energy hub and central target of metabolic regulation. Mitochondria also facilitate proteostasis through pathways such as the ‘mitochondria as guardian in cytosol’ (MAGIC) whereby cytosolic misfolded proteins (MPs) are imported into and degraded inside mitochondria. In...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cold Spring Harbor Laboratory
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10081186/ https://www.ncbi.nlm.nih.gov/pubmed/37034811 http://dx.doi.org/10.1101/2023.03.29.534670 |
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author | Wang, Yuhao Ruan, Linhao Zhu, Jin Zhang, Xi Chih-Chieh Chang, Alexander Tomaszewski, Alexis Li, Rong |
author_facet | Wang, Yuhao Ruan, Linhao Zhu, Jin Zhang, Xi Chih-Chieh Chang, Alexander Tomaszewski, Alexis Li, Rong |
author_sort | Wang, Yuhao |
collection | PubMed |
description | Mitochondria are the cellular energy hub and central target of metabolic regulation. Mitochondria also facilitate proteostasis through pathways such as the ‘mitochondria as guardian in cytosol’ (MAGIC) whereby cytosolic misfolded proteins (MPs) are imported into and degraded inside mitochondria. In this study, a genome-wide screen in yeast uncovered that Snf1, the yeast AMP-activated protein kinase (AMPK), inhibits the import of MPs into mitochondria while promoting mitochondrial biogenesis under glucose starvation. We show that this inhibition requires a downstream transcription factor regulating mitochondrial gene expression and is likely to be conferred through substrate competition and mitochondrial import channel selectivity. We further show that Snf1/AMPK activation protects mitochondrial fitness in yeast and human cells under stress induced by MPs such as those associated with neurodegenerative diseases. |
format | Online Article Text |
id | pubmed-10081186 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Cold Spring Harbor Laboratory |
record_format | MEDLINE/PubMed |
spelling | pubmed-100811862023-04-08 Metabolic regulation of misfolded protein import into mitochondria Wang, Yuhao Ruan, Linhao Zhu, Jin Zhang, Xi Chih-Chieh Chang, Alexander Tomaszewski, Alexis Li, Rong bioRxiv Article Mitochondria are the cellular energy hub and central target of metabolic regulation. Mitochondria also facilitate proteostasis through pathways such as the ‘mitochondria as guardian in cytosol’ (MAGIC) whereby cytosolic misfolded proteins (MPs) are imported into and degraded inside mitochondria. In this study, a genome-wide screen in yeast uncovered that Snf1, the yeast AMP-activated protein kinase (AMPK), inhibits the import of MPs into mitochondria while promoting mitochondrial biogenesis under glucose starvation. We show that this inhibition requires a downstream transcription factor regulating mitochondrial gene expression and is likely to be conferred through substrate competition and mitochondrial import channel selectivity. We further show that Snf1/AMPK activation protects mitochondrial fitness in yeast and human cells under stress induced by MPs such as those associated with neurodegenerative diseases. Cold Spring Harbor Laboratory 2023-08-31 /pmc/articles/PMC10081186/ /pubmed/37034811 http://dx.doi.org/10.1101/2023.03.29.534670 Text en https://creativecommons.org/licenses/by/4.0/This work is licensed under a Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/) , which allows reusers to distribute, remix, adapt, and build upon the material in any medium or format, so long as attribution is given to the creator. The license allows for commercial use. |
spellingShingle | Article Wang, Yuhao Ruan, Linhao Zhu, Jin Zhang, Xi Chih-Chieh Chang, Alexander Tomaszewski, Alexis Li, Rong Metabolic regulation of misfolded protein import into mitochondria |
title | Metabolic regulation of misfolded protein import into mitochondria |
title_full | Metabolic regulation of misfolded protein import into mitochondria |
title_fullStr | Metabolic regulation of misfolded protein import into mitochondria |
title_full_unstemmed | Metabolic regulation of misfolded protein import into mitochondria |
title_short | Metabolic regulation of misfolded protein import into mitochondria |
title_sort | metabolic regulation of misfolded protein import into mitochondria |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10081186/ https://www.ncbi.nlm.nih.gov/pubmed/37034811 http://dx.doi.org/10.1101/2023.03.29.534670 |
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