A Role for Macro-ER-Phagy in ER Quality Control.
The endoplasmic-reticulum quality-control (ERQC) system shuttles misfolded proteins for degradation by the proteasome through the well-defined ER-associated degradation (ERAD) pathway. In contrast, very little is known about the role of autophagy in ERQC. Macro-autophagy, a collection of pathways th...
| Main Authors: | , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2015-07-01
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| Series: | PLoS Genetics |
| Online Access: | http://europepmc.org/articles/PMC4504476?pdf=render |
| _version_ | 1818584598218539008 |
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| author | Zhanna Lipatova Nava Segev |
| author_facet | Zhanna Lipatova Nava Segev |
| author_sort | Zhanna Lipatova |
| collection | DOAJ |
| description | The endoplasmic-reticulum quality-control (ERQC) system shuttles misfolded proteins for degradation by the proteasome through the well-defined ER-associated degradation (ERAD) pathway. In contrast, very little is known about the role of autophagy in ERQC. Macro-autophagy, a collection of pathways that deliver proteins through autophagosomes (APs) for degradation in the lysosome (vacuole in yeast), is mediated by autophagy-specific proteins, Atgs, and regulated by Ypt/Rab GTPases. Until recently, the term ER-phagy was used to describe degradation of ER membrane and proteins in the lysosome under stress: either ER stress induced by drugs or whole-cell stress induced by starvation. These two types of stresses induce micro-ER-phagy, which does not use autophagic organelles and machinery, and non-selective autophagy. Here, we characterize the macro-ER-phagy pathway and uncover its role in ERQC. This pathway delivers 20-50% of certain ER-resident membrane proteins to the vacuole and is further induced to >90% by overexpression of a single integral-membrane protein. Even though such overexpression in cells defective in macro-ER-phagy induces the unfolded-protein response (UPR), UPR is not needed for macro-ER-phagy. We show that macro-ER-phagy is dependent on Atgs and Ypt GTPases and its cargo passes through APs. Moreover, for the first time the role of Atg9, the only integral-membrane core Atg, is uncoupled from that of other core Atgs. Finally, three sequential steps of this pathway are delineated: Atg9-dependent exit from the ER en route to autophagy, Ypt1- and core Atgs-mediated pre-autophagsomal-structure organization, and Ypt51-mediated delivery of APs to the vacuole. |
| first_indexed | 2024-12-16T08:23:43Z |
| format | Article |
| id | doaj.art-a9d7fab90f8f48a8a7cae95e273fa429 |
| institution | Directory Open Access Journal |
| issn | 1553-7390 1553-7404 |
| language | English |
| last_indexed | 2024-12-16T08:23:43Z |
| publishDate | 2015-07-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Genetics |
| spelling | doaj.art-a9d7fab90f8f48a8a7cae95e273fa4292022-12-21T22:38:02ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042015-07-01117e100539010.1371/journal.pgen.1005390A Role for Macro-ER-Phagy in ER Quality Control.Zhanna LipatovaNava SegevThe endoplasmic-reticulum quality-control (ERQC) system shuttles misfolded proteins for degradation by the proteasome through the well-defined ER-associated degradation (ERAD) pathway. In contrast, very little is known about the role of autophagy in ERQC. Macro-autophagy, a collection of pathways that deliver proteins through autophagosomes (APs) for degradation in the lysosome (vacuole in yeast), is mediated by autophagy-specific proteins, Atgs, and regulated by Ypt/Rab GTPases. Until recently, the term ER-phagy was used to describe degradation of ER membrane and proteins in the lysosome under stress: either ER stress induced by drugs or whole-cell stress induced by starvation. These two types of stresses induce micro-ER-phagy, which does not use autophagic organelles and machinery, and non-selective autophagy. Here, we characterize the macro-ER-phagy pathway and uncover its role in ERQC. This pathway delivers 20-50% of certain ER-resident membrane proteins to the vacuole and is further induced to >90% by overexpression of a single integral-membrane protein. Even though such overexpression in cells defective in macro-ER-phagy induces the unfolded-protein response (UPR), UPR is not needed for macro-ER-phagy. We show that macro-ER-phagy is dependent on Atgs and Ypt GTPases and its cargo passes through APs. Moreover, for the first time the role of Atg9, the only integral-membrane core Atg, is uncoupled from that of other core Atgs. Finally, three sequential steps of this pathway are delineated: Atg9-dependent exit from the ER en route to autophagy, Ypt1- and core Atgs-mediated pre-autophagsomal-structure organization, and Ypt51-mediated delivery of APs to the vacuole.http://europepmc.org/articles/PMC4504476?pdf=render |
| spellingShingle | Zhanna Lipatova Nava Segev A Role for Macro-ER-Phagy in ER Quality Control. PLoS Genetics |
| title | A Role for Macro-ER-Phagy in ER Quality Control. |
| title_full | A Role for Macro-ER-Phagy in ER Quality Control. |
| title_fullStr | A Role for Macro-ER-Phagy in ER Quality Control. |
| title_full_unstemmed | A Role for Macro-ER-Phagy in ER Quality Control. |
| title_short | A Role for Macro-ER-Phagy in ER Quality Control. |
| title_sort | role for macro er phagy in er quality control |
| url | http://europepmc.org/articles/PMC4504476?pdf=render |
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