Cargando…
Lysosome damage triggers direct ATG8 conjugation and ATG2 engagement via non-canonical autophagy
Cells harness multiple pathways to maintain lysosome integrity, a central homeostatic process. Damaged lysosomes can be repaired or targeted for degradation by lysophagy, a selective autophagy process involving ATG8/LC3. Here, we describe a parallel ATG8/LC3 response to lysosome damage, mechanistica...
Autores principales: | , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Rockefeller University Press
2023
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10561555/ https://www.ncbi.nlm.nih.gov/pubmed/37796195 http://dx.doi.org/10.1083/jcb.202303078 |
_version_ | 1785117949552492544 |
---|---|
author | Cross, Jake Durgan, Joanne McEwan, David G. Tayler, Matthew Ryan, Kevin M. Florey, Oliver |
author_facet | Cross, Jake Durgan, Joanne McEwan, David G. Tayler, Matthew Ryan, Kevin M. Florey, Oliver |
author_sort | Cross, Jake |
collection | PubMed |
description | Cells harness multiple pathways to maintain lysosome integrity, a central homeostatic process. Damaged lysosomes can be repaired or targeted for degradation by lysophagy, a selective autophagy process involving ATG8/LC3. Here, we describe a parallel ATG8/LC3 response to lysosome damage, mechanistically distinct from lysophagy. Using a comprehensive series of biochemical, pharmacological, and genetic approaches, we show that lysosome damage induces non-canonical autophagy and Conjugation of ATG8s to Single Membranes (CASM). Following damage, ATG8s are rapidly and directly conjugated onto lysosome membranes, independently of ATG13/WIPI2, lipidating to PS (and PE), a molecular hallmark of CASM. Lysosome damage drives V-ATPase V0-V1 association, direct recruitment of ATG16L1 via its WD40-domain/K490A, and is sensitive to Salmonella SopF. Lysosome damage-induced CASM is associated with formation of dynamic, LC3A-positive tubules, and promotes robust LC3A engagement with ATG2, a lipid transfer protein central to lysosome repair. Together, our data identify direct ATG8 conjugation as a rapid response to lysosome damage, with important links to lipid transfer and dynamics. |
format | Online Article Text |
id | pubmed-10561555 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-105615552023-10-10 Lysosome damage triggers direct ATG8 conjugation and ATG2 engagement via non-canonical autophagy Cross, Jake Durgan, Joanne McEwan, David G. Tayler, Matthew Ryan, Kevin M. Florey, Oliver J Cell Biol Report Cells harness multiple pathways to maintain lysosome integrity, a central homeostatic process. Damaged lysosomes can be repaired or targeted for degradation by lysophagy, a selective autophagy process involving ATG8/LC3. Here, we describe a parallel ATG8/LC3 response to lysosome damage, mechanistically distinct from lysophagy. Using a comprehensive series of biochemical, pharmacological, and genetic approaches, we show that lysosome damage induces non-canonical autophagy and Conjugation of ATG8s to Single Membranes (CASM). Following damage, ATG8s are rapidly and directly conjugated onto lysosome membranes, independently of ATG13/WIPI2, lipidating to PS (and PE), a molecular hallmark of CASM. Lysosome damage drives V-ATPase V0-V1 association, direct recruitment of ATG16L1 via its WD40-domain/K490A, and is sensitive to Salmonella SopF. Lysosome damage-induced CASM is associated with formation of dynamic, LC3A-positive tubules, and promotes robust LC3A engagement with ATG2, a lipid transfer protein central to lysosome repair. Together, our data identify direct ATG8 conjugation as a rapid response to lysosome damage, with important links to lipid transfer and dynamics. Rockefeller University Press 2023-10-05 /pmc/articles/PMC10561555/ /pubmed/37796195 http://dx.doi.org/10.1083/jcb.202303078 Text en © 2023 Cross et al. https://creativecommons.org/licenses/by/4.0/This article is available under a Creative Commons License (Attribution 4.0 International, as described at https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Report Cross, Jake Durgan, Joanne McEwan, David G. Tayler, Matthew Ryan, Kevin M. Florey, Oliver Lysosome damage triggers direct ATG8 conjugation and ATG2 engagement via non-canonical autophagy |
title | Lysosome damage triggers direct ATG8 conjugation and ATG2 engagement via non-canonical autophagy |
title_full | Lysosome damage triggers direct ATG8 conjugation and ATG2 engagement via non-canonical autophagy |
title_fullStr | Lysosome damage triggers direct ATG8 conjugation and ATG2 engagement via non-canonical autophagy |
title_full_unstemmed | Lysosome damage triggers direct ATG8 conjugation and ATG2 engagement via non-canonical autophagy |
title_short | Lysosome damage triggers direct ATG8 conjugation and ATG2 engagement via non-canonical autophagy |
title_sort | lysosome damage triggers direct atg8 conjugation and atg2 engagement via non-canonical autophagy |
topic | Report |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10561555/ https://www.ncbi.nlm.nih.gov/pubmed/37796195 http://dx.doi.org/10.1083/jcb.202303078 |
work_keys_str_mv | AT crossjake lysosomedamagetriggersdirectatg8conjugationandatg2engagementvianoncanonicalautophagy AT durganjoanne lysosomedamagetriggersdirectatg8conjugationandatg2engagementvianoncanonicalautophagy AT mcewandavidg lysosomedamagetriggersdirectatg8conjugationandatg2engagementvianoncanonicalautophagy AT taylermatthew lysosomedamagetriggersdirectatg8conjugationandatg2engagementvianoncanonicalautophagy AT ryankevinm lysosomedamagetriggersdirectatg8conjugationandatg2engagementvianoncanonicalautophagy AT floreyoliver lysosomedamagetriggersdirectatg8conjugationandatg2engagementvianoncanonicalautophagy |