Inactive Proteasomes Routed to Autophagic Turnover Are Confined within the Soluble Fraction of the Cell
Previous studies demonstrated that dysfunctional yeast proteasomes accumulate in the insoluble protein deposit (IPOD), described as the final deposition site for amyloidogenic insoluble proteins and that this compartment also mediates proteasome ubiquitination, a prerequisite for their targeted auto...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-12-01
|
| Series: | Biomolecules |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2218-273X/13/1/77 |
| _version_ | 1827628175244394496 |
|---|---|
| author | Keren Friedman Ofri Karmon Uri Fridman Yair Goldberg Ophry Pines Shay Ben-Aroya |
| author_facet | Keren Friedman Ofri Karmon Uri Fridman Yair Goldberg Ophry Pines Shay Ben-Aroya |
| author_sort | Keren Friedman |
| collection | DOAJ |
| description | Previous studies demonstrated that dysfunctional yeast proteasomes accumulate in the insoluble protein deposit (IPOD), described as the final deposition site for amyloidogenic insoluble proteins and that this compartment also mediates proteasome ubiquitination, a prerequisite for their targeted autophagy (proteaphagy). Here, we examined the solubility state of proteasomes subjected to autophagy as a result of their inactivation, or under nutrient starvation. In both cases, only soluble proteasomes could serve as a substrate to autophagy, suggesting a modified model whereby substrates for proteaphagy are dysfunctional proteasomes in their near-native soluble state, and not as previously believed, those sequestered at the IPOD. Furthermore, the insoluble fraction accumulating in the IPOD represents an alternative pathway, enabling the removal of inactive proteasomes that escaped proteaphagy when the system became saturated. Altogether, we suggest that the relocalization of proteasomes to soluble aggregates represents a general stage of proteasome recycling through autophagy. |
| first_indexed | 2024-03-09T13:27:02Z |
| format | Article |
| id | doaj.art-310dade9073f4a66bebfbd7e1dac4cdd |
| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-03-09T13:27:02Z |
| publishDate | 2022-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj.art-310dade9073f4a66bebfbd7e1dac4cdd2023-11-30T21:22:23ZengMDPI AGBiomolecules2218-273X2022-12-011317710.3390/biom13010077Inactive Proteasomes Routed to Autophagic Turnover Are Confined within the Soluble Fraction of the CellKeren Friedman0Ofri Karmon1Uri Fridman2Yair Goldberg3Ophry Pines4Shay Ben-Aroya5Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan 52900, IsraelFaculty of Life Sciences, Bar-Ilan University, Ramat-Gan 52900, IsraelFaculty of Life Sciences, Bar-Ilan University, Ramat-Gan 52900, IsraelFaculty of Life Sciences, Bar-Ilan University, Ramat-Gan 52900, IsraelNUS-HUJ-CREATE Programme and Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 138602, SingaporeFaculty of Life Sciences, Bar-Ilan University, Ramat-Gan 52900, IsraelPrevious studies demonstrated that dysfunctional yeast proteasomes accumulate in the insoluble protein deposit (IPOD), described as the final deposition site for amyloidogenic insoluble proteins and that this compartment also mediates proteasome ubiquitination, a prerequisite for their targeted autophagy (proteaphagy). Here, we examined the solubility state of proteasomes subjected to autophagy as a result of their inactivation, or under nutrient starvation. In both cases, only soluble proteasomes could serve as a substrate to autophagy, suggesting a modified model whereby substrates for proteaphagy are dysfunctional proteasomes in their near-native soluble state, and not as previously believed, those sequestered at the IPOD. Furthermore, the insoluble fraction accumulating in the IPOD represents an alternative pathway, enabling the removal of inactive proteasomes that escaped proteaphagy when the system became saturated. Altogether, we suggest that the relocalization of proteasomes to soluble aggregates represents a general stage of proteasome recycling through autophagy.https://www.mdpi.com/2218-273X/13/1/77proteasomeprotein quality controlautophagy |
| spellingShingle | Keren Friedman Ofri Karmon Uri Fridman Yair Goldberg Ophry Pines Shay Ben-Aroya Inactive Proteasomes Routed to Autophagic Turnover Are Confined within the Soluble Fraction of the Cell Biomolecules proteasome protein quality control autophagy |
| title | Inactive Proteasomes Routed to Autophagic Turnover Are Confined within the Soluble Fraction of the Cell |
| title_full | Inactive Proteasomes Routed to Autophagic Turnover Are Confined within the Soluble Fraction of the Cell |
| title_fullStr | Inactive Proteasomes Routed to Autophagic Turnover Are Confined within the Soluble Fraction of the Cell |
| title_full_unstemmed | Inactive Proteasomes Routed to Autophagic Turnover Are Confined within the Soluble Fraction of the Cell |
| title_short | Inactive Proteasomes Routed to Autophagic Turnover Are Confined within the Soluble Fraction of the Cell |
| title_sort | inactive proteasomes routed to autophagic turnover are confined within the soluble fraction of the cell |
| topic | proteasome protein quality control autophagy |
| url | https://www.mdpi.com/2218-273X/13/1/77 |
| work_keys_str_mv | AT kerenfriedman inactiveproteasomesroutedtoautophagicturnoverareconfinedwithinthesolublefractionofthecell AT ofrikarmon inactiveproteasomesroutedtoautophagicturnoverareconfinedwithinthesolublefractionofthecell AT urifridman inactiveproteasomesroutedtoautophagicturnoverareconfinedwithinthesolublefractionofthecell AT yairgoldberg inactiveproteasomesroutedtoautophagicturnoverareconfinedwithinthesolublefractionofthecell AT ophrypines inactiveproteasomesroutedtoautophagicturnoverareconfinedwithinthesolublefractionofthecell AT shaybenaroya inactiveproteasomesroutedtoautophagicturnoverareconfinedwithinthesolublefractionofthecell |