Degradation of lipid droplets by chimeric autophagy-tethering compounds
dc.contributor.author | Fu, Y | |
dc.contributor.author | Chen, N | |
dc.contributor.author | Wang, Z | |
dc.contributor.author | Luo, Shouqing | |
dc.contributor.author | Ding, Y | |
dc.contributor.author | Lu, B | |
dc.date.accessioned | 2022-01-18T12:23:11Z | |
dc.date.issued | 2021-07-08 | |
dc.identifier.issn | 1001-0602 | |
dc.identifier.issn | 1748-7838 | |
dc.identifier.uri | http://hdl.handle.net/10026.1/18574 | |
dc.description.abstract |
<jats:title>Abstract</jats:title><jats:p>Degrading pathogenic proteins by degrader technologies such as PROTACs (proteolysis-targeting chimeras) provides promising therapeutic strategies, but selective degradation of non-protein pathogenic biomolecules has been challenging. Here, we demonstrate a novel strategy to degrade non-protein biomolecules by autophagy-tethering compounds (ATTECs), using lipid droplets (LDs) as an exemplar target. LDs are ubiquitous cellular structures storing lipids and could be degraded by autophagy. We hypothesized that compounds interacting with both the LDs and the key autophagosome protein LC3 may enhance autophagic degradation of LDs. We designed and synthesized such compounds by connecting LC3-binding molecules to LD-binding probes via a linker. These compounds were capable of clearing LDs almost completely and rescued LD-related phenotypes in cells and in two independent mouse models with hepatic lipidosis. We further confirmed that the mechanism of action of these compounds was mediated through LC3 and autophagic degradation. Our proof-of-concept study demonstrates the capability of degrading LDs by ATTECs. Conceptually, this strategy could be applied to other protein and non-protein targets.</jats:p> | |
dc.format.extent | 965-979 | |
dc.format.medium | Print-Electronic | |
dc.language | en | |
dc.language.iso | en | |
dc.publisher | Shanghai Institutes for Biological Sciences | |
dc.subject | Animals | |
dc.subject | Autophagosomes | |
dc.subject | Autophagy | |
dc.subject | Chimera | |
dc.subject | Lipid Droplets | |
dc.subject | Lipid Metabolism | |
dc.subject | Mice | |
dc.subject | Proteins | |
dc.title | Degradation of lipid droplets by chimeric autophagy-tethering compounds | |
dc.type | journal-article | |
dc.type | Journal Article | |
dc.type | Research Support, Non-U.S. Gov't | |
plymouth.author-url | https://www.ncbi.nlm.nih.gov/pubmed/34239073 | |
plymouth.issue | 9 | |
plymouth.volume | 31 | |
plymouth.publication-status | Published | |
plymouth.journal | Cell Research | |
dc.identifier.doi | 10.1038/s41422-021-00532-7 | |
plymouth.organisational-group | /Plymouth | |
plymouth.organisational-group | /Plymouth/Faculty of Health | |
plymouth.organisational-group | /Plymouth/Faculty of Health/Peninsula Medical School | |
plymouth.organisational-group | /Plymouth/REF 2021 Researchers by UoA | |
plymouth.organisational-group | /Plymouth/REF 2021 Researchers by UoA/UoA01 Clinical Medicine | |
plymouth.organisational-group | /Plymouth/Research Groups | |
plymouth.organisational-group | /Plymouth/Research Groups/Institute of Translational and Stratified Medicine (ITSMED) | |
plymouth.organisational-group | /Plymouth/Research Groups/Institute of Translational and Stratified Medicine (ITSMED)/CBR | |
plymouth.organisational-group | /Plymouth/Users by role | |
plymouth.organisational-group | /Plymouth/Users by role/Academics | |
plymouth.organisational-group | /Plymouth/Users by role/Researchers in ResearchFish submission | |
dc.publisher.place | England | |
dcterms.dateAccepted | 2021-06-18 | |
dc.rights.embargodate | 2022-1-19 | |
dc.identifier.eissn | 1748-7838 | |
dc.rights.embargoperiod | Not known | |
rioxxterms.versionofrecord | 10.1038/s41422-021-00532-7 | |
rioxxterms.licenseref.uri | http://www.rioxx.net/licenses/all-rights-reserved | |
rioxxterms.licenseref.startdate | 2021-07-08 | |
rioxxterms.type | Journal Article/Review |