Distinct types of intramitochondrial protein aggregates protect mitochondria against proteotoxic stress
Summary: Mitochondria consist of hundreds of proteins, most of which are inaccessible to the proteasomal quality control system of the cytosol. How cells stabilize the mitochondrial proteome during challenging conditions remains poorly understood. Here, we show that mitochondria form spatially defin...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2024-04-01
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| Series: | Cell Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124724003462 |
| _version_ | 1797234333045489664 |
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| author | Lea Bertgen Jan-Eric Bökenkamp Tim Schneckmann Christian Koch Markus Räschle Zuzana Storchová Johannes M. Herrmann |
| author_facet | Lea Bertgen Jan-Eric Bökenkamp Tim Schneckmann Christian Koch Markus Räschle Zuzana Storchová Johannes M. Herrmann |
| author_sort | Lea Bertgen |
| collection | DOAJ |
| description | Summary: Mitochondria consist of hundreds of proteins, most of which are inaccessible to the proteasomal quality control system of the cytosol. How cells stabilize the mitochondrial proteome during challenging conditions remains poorly understood. Here, we show that mitochondria form spatially defined protein aggregates as a stress-protecting mechanism. Two different types of intramitochondrial protein aggregates can be distinguished. The mitoribosomal protein Var1 (uS3m) undergoes a stress-induced transition from a soluble, chaperone-stabilized protein that is prevalent under benign conditions to an insoluble, aggregated form upon acute stress. The formation of Var1 bodies stabilizes mitochondrial proteostasis, presumably by sequestration of aggregation-prone proteins. The AAA chaperone Hsp78 is part of a second type of intramitochondrial aggregate that transiently sequesters proteins and promotes their folding or Pim1-mediated degradation. Thus, mitochondrial proteins actively control the formation of distinct types of intramitochondrial protein aggregates, which cooperate to stabilize the mitochondrial proteome during proteotoxic stress conditions. |
| first_indexed | 2024-04-24T16:30:23Z |
| format | Article |
| id | doaj.art-5a25b66705e8486e8dde82236c2f537a |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-04-24T16:30:23Z |
| publishDate | 2024-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-5a25b66705e8486e8dde82236c2f537a2024-03-30T04:39:05ZengElsevierCell Reports2211-12472024-04-01434114018Distinct types of intramitochondrial protein aggregates protect mitochondria against proteotoxic stressLea Bertgen0Jan-Eric Bökenkamp1Tim Schneckmann2Christian Koch3Markus Räschle4Zuzana Storchová5Johannes M. Herrmann6Cell Biology, University of Kaiserslautern, RPTU, Erwin-Schrödinger-Strasse 13, 67663 Kaiserslautern, GermanyMolecular Genetics, University of Kaiserslautern, RPTU, Paul-Ehrlich-Strasse 24, 67663 Kaiserslautern, GermanyCell Biology, University of Kaiserslautern, RPTU, Erwin-Schrödinger-Strasse 13, 67663 Kaiserslautern, GermanyCell Biology, University of Kaiserslautern, RPTU, Erwin-Schrödinger-Strasse 13, 67663 Kaiserslautern, GermanyMolecular Genetics, University of Kaiserslautern, RPTU, Paul-Ehrlich-Strasse 24, 67663 Kaiserslautern, GermanyMolecular Genetics, University of Kaiserslautern, RPTU, Paul-Ehrlich-Strasse 24, 67663 Kaiserslautern, GermanyCell Biology, University of Kaiserslautern, RPTU, Erwin-Schrödinger-Strasse 13, 67663 Kaiserslautern, Germany; Corresponding authorSummary: Mitochondria consist of hundreds of proteins, most of which are inaccessible to the proteasomal quality control system of the cytosol. How cells stabilize the mitochondrial proteome during challenging conditions remains poorly understood. Here, we show that mitochondria form spatially defined protein aggregates as a stress-protecting mechanism. Two different types of intramitochondrial protein aggregates can be distinguished. The mitoribosomal protein Var1 (uS3m) undergoes a stress-induced transition from a soluble, chaperone-stabilized protein that is prevalent under benign conditions to an insoluble, aggregated form upon acute stress. The formation of Var1 bodies stabilizes mitochondrial proteostasis, presumably by sequestration of aggregation-prone proteins. The AAA chaperone Hsp78 is part of a second type of intramitochondrial aggregate that transiently sequesters proteins and promotes their folding or Pim1-mediated degradation. Thus, mitochondrial proteins actively control the formation of distinct types of intramitochondrial protein aggregates, which cooperate to stabilize the mitochondrial proteome during proteotoxic stress conditions.http://www.sciencedirect.com/science/article/pii/S2211124724003462CP: Molecular biologyCP: Cell biology |
| spellingShingle | Lea Bertgen Jan-Eric Bökenkamp Tim Schneckmann Christian Koch Markus Räschle Zuzana Storchová Johannes M. Herrmann Distinct types of intramitochondrial protein aggregates protect mitochondria against proteotoxic stress Cell Reports CP: Molecular biology CP: Cell biology |
| title | Distinct types of intramitochondrial protein aggregates protect mitochondria against proteotoxic stress |
| title_full | Distinct types of intramitochondrial protein aggregates protect mitochondria against proteotoxic stress |
| title_fullStr | Distinct types of intramitochondrial protein aggregates protect mitochondria against proteotoxic stress |
| title_full_unstemmed | Distinct types of intramitochondrial protein aggregates protect mitochondria against proteotoxic stress |
| title_short | Distinct types of intramitochondrial protein aggregates protect mitochondria against proteotoxic stress |
| title_sort | distinct types of intramitochondrial protein aggregates protect mitochondria against proteotoxic stress |
| topic | CP: Molecular biology CP: Cell biology |
| url | http://www.sciencedirect.com/science/article/pii/S2211124724003462 |
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