Cytosolic aggregation of mitochondrial proteins disrupts cellular homeostasis by stimulating the aggregation of other proteins
Mitochondria are organelles with their own genomes, but they rely on the import of nuclear-encoded proteins that are translated by cytosolic ribosomes. Therefore, it is important to understand whether failures in the mitochondrial uptake of these nuclear-encoded proteins can cause proteotoxic stress...
Guardado en:
| Autores principales: | , , , , , , , , , , , |
|---|---|
| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
eLife Sciences Publications Ltd
2021
|
| Materias: | |
| Acceso en línea: | https://doaj.org/article/bde42a68f5f14029a3273e815c975f47 |
| Etiquetas: |
Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
|
| id |
oai:doaj.org-article:bde42a68f5f14029a3273e815c975f47 |
|---|---|
| record_format |
dspace |
| spelling |
oai:doaj.org-article:bde42a68f5f14029a3273e815c975f472021-11-16T08:42:55ZCytosolic aggregation of mitochondrial proteins disrupts cellular homeostasis by stimulating the aggregation of other proteins10.7554/eLife.654842050-084Xe65484https://doaj.org/article/bde42a68f5f14029a3273e815c975f472021-07-01T00:00:00Zhttps://elifesciences.org/articles/65484https://doaj.org/toc/2050-084XMitochondria are organelles with their own genomes, but they rely on the import of nuclear-encoded proteins that are translated by cytosolic ribosomes. Therefore, it is important to understand whether failures in the mitochondrial uptake of these nuclear-encoded proteins can cause proteotoxic stress and identify response mechanisms that may counteract it. Here, we report that upon impairments in mitochondrial protein import, high-risk precursor and immature forms of mitochondrial proteins form aberrant deposits in the cytosol. These deposits then cause further cytosolic accumulation and consequently aggregation of other mitochondrial proteins and disease-related proteins, including α-synuclein and amyloid β. This aggregation triggers a cytosolic protein homeostasis imbalance that is accompanied by specific molecular chaperone responses at both the transcriptomic and protein levels. Altogether, our results provide evidence that mitochondrial dysfunction, specifically protein import defects, contributes to impairments in protein homeostasis, thus revealing a possible molecular mechanism by which mitochondria are involved in neurodegenerative diseases.Urszula NowickaPiotr ChroscickiKaren StroobantsMaria SladowskaMichal TurekBarbara Uszczynska-RatajczakRishika KundraTomasz GoralMichele PerniChristopher M DobsonMichele VendruscoloAgnieszka ChacinskaeLife Sciences Publications Ltdarticlemitochondriaaggregationchaperonesneurodegenerationhomeostasismetastable proteinsMedicineRScienceQBiology (General)QH301-705.5ENeLife, Vol 10 (2021) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
mitochondria aggregation chaperones neurodegeneration homeostasis metastable proteins Medicine R Science Q Biology (General) QH301-705.5 |
| spellingShingle |
mitochondria aggregation chaperones neurodegeneration homeostasis metastable proteins Medicine R Science Q Biology (General) QH301-705.5 Urszula Nowicka Piotr Chroscicki Karen Stroobants Maria Sladowska Michal Turek Barbara Uszczynska-Ratajczak Rishika Kundra Tomasz Goral Michele Perni Christopher M Dobson Michele Vendruscolo Agnieszka Chacinska Cytosolic aggregation of mitochondrial proteins disrupts cellular homeostasis by stimulating the aggregation of other proteins |
| description |
Mitochondria are organelles with their own genomes, but they rely on the import of nuclear-encoded proteins that are translated by cytosolic ribosomes. Therefore, it is important to understand whether failures in the mitochondrial uptake of these nuclear-encoded proteins can cause proteotoxic stress and identify response mechanisms that may counteract it. Here, we report that upon impairments in mitochondrial protein import, high-risk precursor and immature forms of mitochondrial proteins form aberrant deposits in the cytosol. These deposits then cause further cytosolic accumulation and consequently aggregation of other mitochondrial proteins and disease-related proteins, including α-synuclein and amyloid β. This aggregation triggers a cytosolic protein homeostasis imbalance that is accompanied by specific molecular chaperone responses at both the transcriptomic and protein levels. Altogether, our results provide evidence that mitochondrial dysfunction, specifically protein import defects, contributes to impairments in protein homeostasis, thus revealing a possible molecular mechanism by which mitochondria are involved in neurodegenerative diseases. |
| format |
article |
| author |
Urszula Nowicka Piotr Chroscicki Karen Stroobants Maria Sladowska Michal Turek Barbara Uszczynska-Ratajczak Rishika Kundra Tomasz Goral Michele Perni Christopher M Dobson Michele Vendruscolo Agnieszka Chacinska |
| author_facet |
Urszula Nowicka Piotr Chroscicki Karen Stroobants Maria Sladowska Michal Turek Barbara Uszczynska-Ratajczak Rishika Kundra Tomasz Goral Michele Perni Christopher M Dobson Michele Vendruscolo Agnieszka Chacinska |
| author_sort |
Urszula Nowicka |
| title |
Cytosolic aggregation of mitochondrial proteins disrupts cellular homeostasis by stimulating the aggregation of other proteins |
| title_short |
Cytosolic aggregation of mitochondrial proteins disrupts cellular homeostasis by stimulating the aggregation of other proteins |
| title_full |
Cytosolic aggregation of mitochondrial proteins disrupts cellular homeostasis by stimulating the aggregation of other proteins |
| title_fullStr |
Cytosolic aggregation of mitochondrial proteins disrupts cellular homeostasis by stimulating the aggregation of other proteins |
| title_full_unstemmed |
Cytosolic aggregation of mitochondrial proteins disrupts cellular homeostasis by stimulating the aggregation of other proteins |
| title_sort |
cytosolic aggregation of mitochondrial proteins disrupts cellular homeostasis by stimulating the aggregation of other proteins |
| publisher |
eLife Sciences Publications Ltd |
| publishDate |
2021 |
| url |
https://doaj.org/article/bde42a68f5f14029a3273e815c975f47 |
| work_keys_str_mv |
AT urszulanowicka cytosolicaggregationofmitochondrialproteinsdisruptscellularhomeostasisbystimulatingtheaggregationofotherproteins AT piotrchroscicki cytosolicaggregationofmitochondrialproteinsdisruptscellularhomeostasisbystimulatingtheaggregationofotherproteins AT karenstroobants cytosolicaggregationofmitochondrialproteinsdisruptscellularhomeostasisbystimulatingtheaggregationofotherproteins AT mariasladowska cytosolicaggregationofmitochondrialproteinsdisruptscellularhomeostasisbystimulatingtheaggregationofotherproteins AT michalturek cytosolicaggregationofmitochondrialproteinsdisruptscellularhomeostasisbystimulatingtheaggregationofotherproteins AT barbarauszczynskaratajczak cytosolicaggregationofmitochondrialproteinsdisruptscellularhomeostasisbystimulatingtheaggregationofotherproteins AT rishikakundra cytosolicaggregationofmitochondrialproteinsdisruptscellularhomeostasisbystimulatingtheaggregationofotherproteins AT tomaszgoral cytosolicaggregationofmitochondrialproteinsdisruptscellularhomeostasisbystimulatingtheaggregationofotherproteins AT micheleperni cytosolicaggregationofmitochondrialproteinsdisruptscellularhomeostasisbystimulatingtheaggregationofotherproteins AT christophermdobson cytosolicaggregationofmitochondrialproteinsdisruptscellularhomeostasisbystimulatingtheaggregationofotherproteins AT michelevendruscolo cytosolicaggregationofmitochondrialproteinsdisruptscellularhomeostasisbystimulatingtheaggregationofotherproteins AT agnieszkachacinska cytosolicaggregationofmitochondrialproteinsdisruptscellularhomeostasisbystimulatingtheaggregationofotherproteins |
| _version_ |
1718426629035786240 |