The ER-phagy receptor FAM134B is targeted by Salmonella Typhimurium to promote infection
Abstract Macroautophagy/autophagy is a key catabolic-recycling pathway that can selectively target damaged organelles or invading pathogens for degradation. The selective autophagic degradation of the endoplasmic reticulum (hereafter referred to as ER-phagy) is a homeostatic mechanism, controlling E...
Saved in:
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2025-03-01
|
| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-58035-7 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850207915334434816 |
|---|---|
| author | Damián Gatica Reham M. Alsaadi Rayan El Hamra Boran Li Rudolf Mueller Makoto Miyazaki Qiming Sun Subash Sad Ryan C. Russell |
| author_facet | Damián Gatica Reham M. Alsaadi Rayan El Hamra Boran Li Rudolf Mueller Makoto Miyazaki Qiming Sun Subash Sad Ryan C. Russell |
| author_sort | Damián Gatica |
| collection | DOAJ |
| description | Abstract Macroautophagy/autophagy is a key catabolic-recycling pathway that can selectively target damaged organelles or invading pathogens for degradation. The selective autophagic degradation of the endoplasmic reticulum (hereafter referred to as ER-phagy) is a homeostatic mechanism, controlling ER size, the removal of misfolded protein aggregates, and organelle damage. ER-phagy can also be stimulated by pathogen infection. However, the link between ER-phagy and bacterial infection remains poorly understood, as are the mechanisms evolved by pathogens to escape the effects of ER-phagy. Here, we show that Salmonella enterica serovar Typhimurium inhibits ER-phagy by targeting the ER-phagy receptor FAM134B, leading to a pronounced increase in Salmonella burden after invasion. Salmonella prevents FAM134B oligomerization, which is required for efficient ER-phagy. FAM134B knock-out raises intracellular Salmonella number, while FAM134B activation reduces Salmonella burden. Additionally, we found that Salmonella targets FAM134B through the bacterial effector SopF to enhance intracellular survival through ER-phagy inhibition. Furthermore, FAM134B knock-out mice infected with Salmonella presented severe intestinal damage and increased bacterial burden. These results provide mechanistic insight into the interplay between ER-phagy and bacterial infection, highlighting a key role for FAM134B in innate immunity. |
| format | Article |
| id | doaj-art-b254d16ad7504a41b109f9fc0c6ac4e4 |
| institution | OA Journals |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-b254d16ad7504a41b109f9fc0c6ac4e42025-08-20T02:10:21ZengNature PortfolioNature Communications2041-17232025-03-0116111810.1038/s41467-025-58035-7The ER-phagy receptor FAM134B is targeted by Salmonella Typhimurium to promote infectionDamián Gatica0Reham M. Alsaadi1Rayan El Hamra2Boran Li3Rudolf Mueller4Makoto Miyazaki5Qiming Sun6Subash Sad7Ryan C. Russell8Department of Cellular and Molecular Medicine, University of OttawaDepartment of Cellular and Molecular Medicine, University of OttawaDepartment of Biochemistry, Microbiology and Immunology, University of OttawaInternational Institutes of Medicine, The Fourth Affiliated Hospital of Zhejiang University School of MedicineDepartment of Pathology and Laboratory Medicine, Faculty of Medicine, University of OttawaDivision of Renal Diseases and Hypertension, Department of Medicine, University of Colorado DenverInternational Institutes of Medicine, The Fourth Affiliated Hospital of Zhejiang University School of MedicineDepartment of Biochemistry, Microbiology and Immunology, University of OttawaDepartment of Cellular and Molecular Medicine, University of OttawaAbstract Macroautophagy/autophagy is a key catabolic-recycling pathway that can selectively target damaged organelles or invading pathogens for degradation. The selective autophagic degradation of the endoplasmic reticulum (hereafter referred to as ER-phagy) is a homeostatic mechanism, controlling ER size, the removal of misfolded protein aggregates, and organelle damage. ER-phagy can also be stimulated by pathogen infection. However, the link between ER-phagy and bacterial infection remains poorly understood, as are the mechanisms evolved by pathogens to escape the effects of ER-phagy. Here, we show that Salmonella enterica serovar Typhimurium inhibits ER-phagy by targeting the ER-phagy receptor FAM134B, leading to a pronounced increase in Salmonella burden after invasion. Salmonella prevents FAM134B oligomerization, which is required for efficient ER-phagy. FAM134B knock-out raises intracellular Salmonella number, while FAM134B activation reduces Salmonella burden. Additionally, we found that Salmonella targets FAM134B through the bacterial effector SopF to enhance intracellular survival through ER-phagy inhibition. Furthermore, FAM134B knock-out mice infected with Salmonella presented severe intestinal damage and increased bacterial burden. These results provide mechanistic insight into the interplay between ER-phagy and bacterial infection, highlighting a key role for FAM134B in innate immunity.https://doi.org/10.1038/s41467-025-58035-7 |
| spellingShingle | Damián Gatica Reham M. Alsaadi Rayan El Hamra Boran Li Rudolf Mueller Makoto Miyazaki Qiming Sun Subash Sad Ryan C. Russell The ER-phagy receptor FAM134B is targeted by Salmonella Typhimurium to promote infection Nature Communications |
| title | The ER-phagy receptor FAM134B is targeted by Salmonella Typhimurium to promote infection |
| title_full | The ER-phagy receptor FAM134B is targeted by Salmonella Typhimurium to promote infection |
| title_fullStr | The ER-phagy receptor FAM134B is targeted by Salmonella Typhimurium to promote infection |
| title_full_unstemmed | The ER-phagy receptor FAM134B is targeted by Salmonella Typhimurium to promote infection |
| title_short | The ER-phagy receptor FAM134B is targeted by Salmonella Typhimurium to promote infection |
| title_sort | er phagy receptor fam134b is targeted by salmonella typhimurium to promote infection |
| url | https://doi.org/10.1038/s41467-025-58035-7 |
| work_keys_str_mv | AT damiangatica theerphagyreceptorfam134bistargetedbysalmonellatyphimuriumtopromoteinfection AT rehammalsaadi theerphagyreceptorfam134bistargetedbysalmonellatyphimuriumtopromoteinfection AT rayanelhamra theerphagyreceptorfam134bistargetedbysalmonellatyphimuriumtopromoteinfection AT boranli theerphagyreceptorfam134bistargetedbysalmonellatyphimuriumtopromoteinfection AT rudolfmueller theerphagyreceptorfam134bistargetedbysalmonellatyphimuriumtopromoteinfection AT makotomiyazaki theerphagyreceptorfam134bistargetedbysalmonellatyphimuriumtopromoteinfection AT qimingsun theerphagyreceptorfam134bistargetedbysalmonellatyphimuriumtopromoteinfection AT subashsad theerphagyreceptorfam134bistargetedbysalmonellatyphimuriumtopromoteinfection AT ryancrussell theerphagyreceptorfam134bistargetedbysalmonellatyphimuriumtopromoteinfection AT damiangatica erphagyreceptorfam134bistargetedbysalmonellatyphimuriumtopromoteinfection AT rehammalsaadi erphagyreceptorfam134bistargetedbysalmonellatyphimuriumtopromoteinfection AT rayanelhamra erphagyreceptorfam134bistargetedbysalmonellatyphimuriumtopromoteinfection AT boranli erphagyreceptorfam134bistargetedbysalmonellatyphimuriumtopromoteinfection AT rudolfmueller erphagyreceptorfam134bistargetedbysalmonellatyphimuriumtopromoteinfection AT makotomiyazaki erphagyreceptorfam134bistargetedbysalmonellatyphimuriumtopromoteinfection AT qimingsun erphagyreceptorfam134bistargetedbysalmonellatyphimuriumtopromoteinfection AT subashsad erphagyreceptorfam134bistargetedbysalmonellatyphimuriumtopromoteinfection AT ryancrussell erphagyreceptorfam134bistargetedbysalmonellatyphimuriumtopromoteinfection |