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ATG12-ATG3 Interacts with Alix to Promote Basal Autophagic Flux and Late Endosome Function
The ubiquitin-like molecule ATG12 is required for the early steps of autophagy. Recently, we identified ATG3, the E2-like enzyme required for LC3 lipidation during autophagy, as an ATG12 conjugation target. Here, we demonstrate that cells lacking ATG12-ATG3 have impaired basal autophagic flux, accum...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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2015
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4344874/ https://www.ncbi.nlm.nih.gov/pubmed/25686249 http://dx.doi.org/10.1038/ncb3112 |
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author | Murrow, Lyndsay Malhotra, Ritu Debnath, Jayanta |
author_facet | Murrow, Lyndsay Malhotra, Ritu Debnath, Jayanta |
author_sort | Murrow, Lyndsay |
collection | PubMed |
description | The ubiquitin-like molecule ATG12 is required for the early steps of autophagy. Recently, we identified ATG3, the E2-like enzyme required for LC3 lipidation during autophagy, as an ATG12 conjugation target. Here, we demonstrate that cells lacking ATG12-ATG3 have impaired basal autophagic flux, accumulation of perinuclear late endosomes, and impaired endolysosomal trafficking. Furthermore, we identify an interaction between ATG12-ATG3 and the ESCRT-associated protein Alix (also known as PDCD6IP) and demonstrate that ATG12-ATG3 controls multiple Alix-dependent processes including late endosome distribution, exosome biogenesis, and viral budding. Lastly, similar to ATG12-ATG3, Alix is functionally required for efficient basal, but not starvation-induced, autophagy. Overall, these results identify a link between the core autophagy and ESCRT machineries and uncover a role for ATG12-ATG3 in late endosome function that is distinct from the canonical role of either ATG in autophagosome formation. |
format | Online Article Text |
id | pubmed-4344874 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
record_format | MEDLINE/PubMed |
spelling | pubmed-43448742015-09-01 ATG12-ATG3 Interacts with Alix to Promote Basal Autophagic Flux and Late Endosome Function Murrow, Lyndsay Malhotra, Ritu Debnath, Jayanta Nat Cell Biol Article The ubiquitin-like molecule ATG12 is required for the early steps of autophagy. Recently, we identified ATG3, the E2-like enzyme required for LC3 lipidation during autophagy, as an ATG12 conjugation target. Here, we demonstrate that cells lacking ATG12-ATG3 have impaired basal autophagic flux, accumulation of perinuclear late endosomes, and impaired endolysosomal trafficking. Furthermore, we identify an interaction between ATG12-ATG3 and the ESCRT-associated protein Alix (also known as PDCD6IP) and demonstrate that ATG12-ATG3 controls multiple Alix-dependent processes including late endosome distribution, exosome biogenesis, and viral budding. Lastly, similar to ATG12-ATG3, Alix is functionally required for efficient basal, but not starvation-induced, autophagy. Overall, these results identify a link between the core autophagy and ESCRT machineries and uncover a role for ATG12-ATG3 in late endosome function that is distinct from the canonical role of either ATG in autophagosome formation. 2015-02-16 2015-03 /pmc/articles/PMC4344874/ /pubmed/25686249 http://dx.doi.org/10.1038/ncb3112 Text en http://www.nature.com/authors/editorial_policies/license.html#terms Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms |
spellingShingle | Article Murrow, Lyndsay Malhotra, Ritu Debnath, Jayanta ATG12-ATG3 Interacts with Alix to Promote Basal Autophagic Flux and Late Endosome Function |
title | ATG12-ATG3 Interacts with Alix to Promote Basal Autophagic Flux and Late Endosome Function |
title_full | ATG12-ATG3 Interacts with Alix to Promote Basal Autophagic Flux and Late Endosome Function |
title_fullStr | ATG12-ATG3 Interacts with Alix to Promote Basal Autophagic Flux and Late Endosome Function |
title_full_unstemmed | ATG12-ATG3 Interacts with Alix to Promote Basal Autophagic Flux and Late Endosome Function |
title_short | ATG12-ATG3 Interacts with Alix to Promote Basal Autophagic Flux and Late Endosome Function |
title_sort | atg12-atg3 interacts with alix to promote basal autophagic flux and late endosome function |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4344874/ https://www.ncbi.nlm.nih.gov/pubmed/25686249 http://dx.doi.org/10.1038/ncb3112 |
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