Sequestration of translation initiation factors in p62 condensates
Summary: Selective autophagy mediates the removal of harmful material from the cytoplasm. This cargo material is selected by cargo receptors, which orchestrate its sequestration within double-membrane autophagosomes and subsequent lysosomal degradation. The cargo receptor p62/SQSTM1 is present in cy...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2023-12-01
|
| Series: | Cell Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124723015954 |
| _version_ | 1827584905012314112 |
|---|---|
| author | Alberto Danieli Georg Vucak Manuela Baccarini Sascha Martens |
| author_facet | Alberto Danieli Georg Vucak Manuela Baccarini Sascha Martens |
| author_sort | Alberto Danieli |
| collection | DOAJ |
| description | Summary: Selective autophagy mediates the removal of harmful material from the cytoplasm. This cargo material is selected by cargo receptors, which orchestrate its sequestration within double-membrane autophagosomes and subsequent lysosomal degradation. The cargo receptor p62/SQSTM1 is present in cytoplasmic condensates, and a fraction of them are constantly delivered into lysosomes. However, the molecular composition of the p62 condensates is incompletely understood. To obtain insights into their composition, we develop a method to isolate these condensates and find that p62 condensates are enriched in components of the translation machinery. Furthermore, p62 interacts with translation initiation factors, and eukaryotic initiation factor 2α (eIF2α) and eIF4E are degraded by autophagy in a p62-dependent manner. Thus, p62-mediated autophagy may in part be linked to down-regulation of translation initiation. The p62 condensate isolation protocol developed here may facilitate the study of their contribution to cellular quality control and their roles in health and disease. |
| first_indexed | 2024-03-08T23:38:00Z |
| format | Article |
| id | doaj.art-ab634fcf79e74db9afc6897c181e658f |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-03-08T23:38:00Z |
| publishDate | 2023-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-ab634fcf79e74db9afc6897c181e658f2023-12-14T05:22:45ZengElsevierCell Reports2211-12472023-12-014212113583Sequestration of translation initiation factors in p62 condensatesAlberto Danieli0Georg Vucak1Manuela Baccarini2Sascha Martens3Max Perutz Labs, Vienna Biocenter Campus (VBC), Dr.-Bohr-Gasse 9, 1030 Vienna, Austria; University of Vienna, Center for Molecular Biology, Department of Biochemistry and Cell Biology, Dr.-Bohr-Gasse 9, 1030 Vienna, Austria; Vienna BioCenter PhD Program, Doctoral School of the University of Vienna and Medical University of Vienna, Campus-Vienna-Biocenter 1, 1030 Vienna, Austria; Corresponding authorMax Perutz Labs, Vienna Biocenter Campus (VBC), Dr.-Bohr-Gasse 9, 1030 Vienna, Austria; Vienna BioCenter PhD Program, Doctoral School of the University of Vienna and Medical University of Vienna, Campus-Vienna-Biocenter 1, 1030 Vienna, Austria; University of Vienna, Center for Molecular Biology, Department of Microbiology, Immunobiology and Genetics, Dr.-Bohr-Gasse 9, 1030 Vienna, AustriaMax Perutz Labs, Vienna Biocenter Campus (VBC), Dr.-Bohr-Gasse 9, 1030 Vienna, Austria; University of Vienna, Center for Molecular Biology, Department of Microbiology, Immunobiology and Genetics, Dr.-Bohr-Gasse 9, 1030 Vienna, AustriaMax Perutz Labs, Vienna Biocenter Campus (VBC), Dr.-Bohr-Gasse 9, 1030 Vienna, Austria; University of Vienna, Center for Molecular Biology, Department of Biochemistry and Cell Biology, Dr.-Bohr-Gasse 9, 1030 Vienna, Austria; Corresponding authorSummary: Selective autophagy mediates the removal of harmful material from the cytoplasm. This cargo material is selected by cargo receptors, which orchestrate its sequestration within double-membrane autophagosomes and subsequent lysosomal degradation. The cargo receptor p62/SQSTM1 is present in cytoplasmic condensates, and a fraction of them are constantly delivered into lysosomes. However, the molecular composition of the p62 condensates is incompletely understood. To obtain insights into their composition, we develop a method to isolate these condensates and find that p62 condensates are enriched in components of the translation machinery. Furthermore, p62 interacts with translation initiation factors, and eukaryotic initiation factor 2α (eIF2α) and eIF4E are degraded by autophagy in a p62-dependent manner. Thus, p62-mediated autophagy may in part be linked to down-regulation of translation initiation. The p62 condensate isolation protocol developed here may facilitate the study of their contribution to cellular quality control and their roles in health and disease.http://www.sciencedirect.com/science/article/pii/S2211124723015954CP: Cell biologyCP: Molecular biology |
| spellingShingle | Alberto Danieli Georg Vucak Manuela Baccarini Sascha Martens Sequestration of translation initiation factors in p62 condensates Cell Reports CP: Cell biology CP: Molecular biology |
| title | Sequestration of translation initiation factors in p62 condensates |
| title_full | Sequestration of translation initiation factors in p62 condensates |
| title_fullStr | Sequestration of translation initiation factors in p62 condensates |
| title_full_unstemmed | Sequestration of translation initiation factors in p62 condensates |
| title_short | Sequestration of translation initiation factors in p62 condensates |
| title_sort | sequestration of translation initiation factors in p62 condensates |
| topic | CP: Cell biology CP: Molecular biology |
| url | http://www.sciencedirect.com/science/article/pii/S2211124723015954 |
| work_keys_str_mv | AT albertodanieli sequestrationoftranslationinitiationfactorsinp62condensates AT georgvucak sequestrationoftranslationinitiationfactorsinp62condensates AT manuelabaccarini sequestrationoftranslationinitiationfactorsinp62condensates AT saschamartens sequestrationoftranslationinitiationfactorsinp62condensates |