Cargando…
Solid-phase inclusion as a mechanism for regulating unfolded proteins in the mitochondrial matrix
Proteostasis declines with age, characterized by the accumulation of unfolded or damaged proteins. Recent studies suggest that proteins constituting pathological inclusions in neurodegenerative diseases also enter and accumulate in mitochondria. How unfolded proteins are managed within mitochondria...
Autores principales: | , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Association for the Advancement of Science
2020
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7406381/ https://www.ncbi.nlm.nih.gov/pubmed/32821848 http://dx.doi.org/10.1126/sciadv.abc7288 |
_version_ | 1783567407742189568 |
---|---|
author | Ruan, Linhao McNamara, Joshua T. Zhang, Xi Chang, Alexander Chih-Chieh Zhu, Jin Dong, Yi Sun, Gordon Peterson, Amy Na, Chan Hyun Li, Rong |
author_facet | Ruan, Linhao McNamara, Joshua T. Zhang, Xi Chang, Alexander Chih-Chieh Zhu, Jin Dong, Yi Sun, Gordon Peterson, Amy Na, Chan Hyun Li, Rong |
author_sort | Ruan, Linhao |
collection | PubMed |
description | Proteostasis declines with age, characterized by the accumulation of unfolded or damaged proteins. Recent studies suggest that proteins constituting pathological inclusions in neurodegenerative diseases also enter and accumulate in mitochondria. How unfolded proteins are managed within mitochondria remains unclear. Here, we found that excessive unfolded proteins in the mitochondrial matrix of yeast cells are consolidated into solid-phase inclusions, which we term deposits of unfolded mitochondrial proteins (DUMP). Formation of DUMP occurs in mitochondria near endoplasmic reticulum–mitochondria contact sites and is regulated by mitochondrial proteins controlling the production of cytidine 5′-diphosphate–diacylglycerol. DUMP formation is age dependent but accelerated by exogenous unfolded proteins. Many enzymes of the tricarboxylic acid cycle were enriched in DUMP. During yeast cell division, DUMP formation is necessary for asymmetric inheritance of damaged mitochondrial proteins between mother and daughter cells. We provide evidence that DUMP-like structures may be induced by excessive unfolded proteins in human cells. |
format | Online Article Text |
id | pubmed-7406381 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | American Association for the Advancement of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-74063812020-08-19 Solid-phase inclusion as a mechanism for regulating unfolded proteins in the mitochondrial matrix Ruan, Linhao McNamara, Joshua T. Zhang, Xi Chang, Alexander Chih-Chieh Zhu, Jin Dong, Yi Sun, Gordon Peterson, Amy Na, Chan Hyun Li, Rong Sci Adv Research Articles Proteostasis declines with age, characterized by the accumulation of unfolded or damaged proteins. Recent studies suggest that proteins constituting pathological inclusions in neurodegenerative diseases also enter and accumulate in mitochondria. How unfolded proteins are managed within mitochondria remains unclear. Here, we found that excessive unfolded proteins in the mitochondrial matrix of yeast cells are consolidated into solid-phase inclusions, which we term deposits of unfolded mitochondrial proteins (DUMP). Formation of DUMP occurs in mitochondria near endoplasmic reticulum–mitochondria contact sites and is regulated by mitochondrial proteins controlling the production of cytidine 5′-diphosphate–diacylglycerol. DUMP formation is age dependent but accelerated by exogenous unfolded proteins. Many enzymes of the tricarboxylic acid cycle were enriched in DUMP. During yeast cell division, DUMP formation is necessary for asymmetric inheritance of damaged mitochondrial proteins between mother and daughter cells. We provide evidence that DUMP-like structures may be induced by excessive unfolded proteins in human cells. American Association for the Advancement of Science 2020-08-05 /pmc/articles/PMC7406381/ /pubmed/32821848 http://dx.doi.org/10.1126/sciadv.abc7288 Text en Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC). https://creativecommons.org/licenses/by-nc/4.0/ https://creativecommons.org/licenses/by-nc/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial license (https://creativecommons.org/licenses/by-nc/4.0/) , which permits use, distribution, and reproduction in any medium, so long as the resultant use is not for commercial advantage and provided the original work is properly cited. |
spellingShingle | Research Articles Ruan, Linhao McNamara, Joshua T. Zhang, Xi Chang, Alexander Chih-Chieh Zhu, Jin Dong, Yi Sun, Gordon Peterson, Amy Na, Chan Hyun Li, Rong Solid-phase inclusion as a mechanism for regulating unfolded proteins in the mitochondrial matrix |
title | Solid-phase inclusion as a mechanism for regulating unfolded proteins in the mitochondrial matrix |
title_full | Solid-phase inclusion as a mechanism for regulating unfolded proteins in the mitochondrial matrix |
title_fullStr | Solid-phase inclusion as a mechanism for regulating unfolded proteins in the mitochondrial matrix |
title_full_unstemmed | Solid-phase inclusion as a mechanism for regulating unfolded proteins in the mitochondrial matrix |
title_short | Solid-phase inclusion as a mechanism for regulating unfolded proteins in the mitochondrial matrix |
title_sort | solid-phase inclusion as a mechanism for regulating unfolded proteins in the mitochondrial matrix |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7406381/ https://www.ncbi.nlm.nih.gov/pubmed/32821848 http://dx.doi.org/10.1126/sciadv.abc7288 |
work_keys_str_mv | AT ruanlinhao solidphaseinclusionasamechanismforregulatingunfoldedproteinsinthemitochondrialmatrix AT mcnamarajoshuat solidphaseinclusionasamechanismforregulatingunfoldedproteinsinthemitochondrialmatrix AT zhangxi solidphaseinclusionasamechanismforregulatingunfoldedproteinsinthemitochondrialmatrix AT changalexanderchihchieh solidphaseinclusionasamechanismforregulatingunfoldedproteinsinthemitochondrialmatrix AT zhujin solidphaseinclusionasamechanismforregulatingunfoldedproteinsinthemitochondrialmatrix AT dongyi solidphaseinclusionasamechanismforregulatingunfoldedproteinsinthemitochondrialmatrix AT sungordon solidphaseinclusionasamechanismforregulatingunfoldedproteinsinthemitochondrialmatrix AT petersonamy solidphaseinclusionasamechanismforregulatingunfoldedproteinsinthemitochondrialmatrix AT nachanhyun solidphaseinclusionasamechanismforregulatingunfoldedproteinsinthemitochondrialmatrix AT lirong solidphaseinclusionasamechanismforregulatingunfoldedproteinsinthemitochondrialmatrix |