elib
DLR-Header
DLR-Logo -> http://www.dlr.de
DLR Portal Home | Imprint | Privacy Policy | Contact | Deutsch
Fontsize: [-] Text [+]

Proteasomes of Autophagy-Deficient Cells Exhibit Alterations in Regulatory Proteins and a Marked Reduction in Activity

Xiong, Qiuhong and Feng, Rong and Fischer, Sarah and Karow, Malte and Stumpf, Maria and Meßling, Susanne and Nitz, Leonie and Müller, Stefan and Clemen, Christoph S. and Song, Ning and Li, Ping (2023) Proteasomes of Autophagy-Deficient Cells Exhibit Alterations in Regulatory Proteins and a Marked Reduction in Activity. Cells, 12 (11), p. 1514. Multidisciplinary Digital Publishing Institute (MDPI). doi: 10.3390/cells12111514. ISSN 2073-4409.

[img] PDF - Published version
2MB

Official URL: https://doi.org/10.3390/cells12111514

Abstract

Autophagy and the ubiquitin proteasome system are the two major processes for the clearance and recycling of proteins and organelles in eukaryotic cells. Evidence is accumulating that there is extensive crosstalk between the two pathways, but the underlying mechanisms are still unclear. We previously found that autophagy 9 (ATG9) and 16 (ATG16) proteins are crucial for full proteasomal activity in the unicellular amoeba Dictyostelium discoideum. In comparison to AX2 wild-type cells, ATG9- and ATG16- cells displayed a 60 percent, and ATG9-/16- cells a 90 percent decrease in proteasomal activity. Mutant cells also showed a significant increase in poly-ubiquitinated proteins and contained large ubiquitin-positive protein aggregates. Here, we focus on possible reasons for these results. Reanalysis of published tandem mass tag-based quantitative proteomic results of AX2, ATG9-, ATG16-, and ATG9-/16- cells revealed no change in the abundance of proteasomal subunits. To identify possible differences in proteasome-associated proteins, we generated AX2 wildtype and ATG16- cells expressing the 20S proteasomal subunit PSMA4 as GFP-tagged fusion protein, and performed co-immunoprecipitation experiments followed by mass spectrometric analysis. The results revealed no significant differences in the abundance of proteasomes between the two strains. However, we found enrichment as well as depletion of proteasomal regulators and differences in the ubiquitination of associated proteins for ATG16-, as compared to AX2 cells. Recently, proteaphagy has been described as a means to replace non-functional proteasomes. We propose that autophagy-deficient D. discoideum mutants suffer from inefficient proteaphagy, which results in the accumulation of modified, less-active, and also of inactive, proteasomes. As a consequence, these cells exhibit a dramatic decrease in proteasomal activity and deranged protein homeostasis.

Item URL in elib:https://elib.dlr.de/198845/
Document Type:Article
Title:Proteasomes of Autophagy-Deficient Cells Exhibit Alterations in Regulatory Proteins and a Marked Reduction in Activity
Authors:
AuthorsInstitution or Email of AuthorsAuthor's ORCID iDORCID Put Code
Xiong, QiuhongShanxi University, Institutes of Biomedical Sciences, Key Laboratory of Medical Molecular Cell Biology, Taiyuan, ChinaUNSPECIFIEDUNSPECIFIED
Feng, RongShanxi University, Institutes of Biomedical Sciences, Key Laboratory of Medical Molecular Cell Biology, Taiyuan, ChinaUNSPECIFIEDUNSPECIFIED
Fischer, SarahUniversity of Cologne, Medical Faculty, Institute of Biochemistry, Cologne, GermanyUNSPECIFIEDUNSPECIFIED
Karow, MalteUniversity of Cologne, Medical Faculty, Institute of Biochemistry, Cologne, GermanyUNSPECIFIEDUNSPECIFIED
Stumpf, MariaUniversity of Cologne, Medical Faculty, Institute of Biochemistry, Cologne, GermanyUNSPECIFIEDUNSPECIFIED
Meßling, SusanneUniversity of Cologne, Medical Faculty, Institute of Biochemistry, Cologne, GermanyUNSPECIFIEDUNSPECIFIED
Nitz, LeonieUniversity of Cologne, Medical Faculty, Institute of Biochemistry, Cologne, GermanyUNSPECIFIEDUNSPECIFIED
Müller, StefanUniversity of Cologne, Medical Faculty, Center for Molecular Medicine, Cologne, GermanyUNSPECIFIEDUNSPECIFIED
Clemen, Christoph S.German Aerospace Center (DLR), Institute of Aerospace Medicine, Gravitational Biology, Colognehttps://orcid.org/0000-0002-1291-4219UNSPECIFIED
Song, NingShanxi University, Institutes of Biomedical Sciences, Key Laboratory of Medical Molecular Cell Biology, Taiyuan, ChinaUNSPECIFIEDUNSPECIFIED
Li, PingShanxi University, Institutes of Biomedical Sciences, Key Laboratory of Medical Molecular Cell Biology, Taiyuan, ChinaUNSPECIFIEDUNSPECIFIED
Date:30 May 2023
Journal or Publication Title:Cells
Refereed publication:Yes
Open Access:Yes
Gold Open Access:Yes
In SCOPUS:Yes
In ISI Web of Science:Yes
Volume:12
DOI:10.3390/cells12111514
Page Range:p. 1514
Publisher:Multidisciplinary Digital Publishing Institute (MDPI)
ISSN:2073-4409
Status:Published
Keywords:Autophagy, ubiquitin proteasome system (UPS), Dictyostelium, ATG9, ATG16
HGF - Research field:Aeronautics, Space and Transport
HGF - Program:Space
HGF - Program Themes:Research under Space Conditions
DLR - Research area:Raumfahrt
DLR - Program:R FR - Research under Space Conditions
DLR - Research theme (Project):R - Gravisensorics
Location: Köln-Porz
Institutes and Institutions:Institute of Aerospace Medicine > Gravitational Biology
Deposited By: Chiodo, Annette
Deposited On:15 Nov 2023 12:03
Last Modified:22 Nov 2023 10:33

Repository Staff Only: item control page

Browse
Search
Help & Contact
Information
electronic library is running on EPrints 3.3.12
Website and database design: Copyright © German Aerospace Center (DLR). All rights reserved.