A Role for Macro-ER-Phagy in ER Quality Control
ER-quality control (ERQC) ensures delivery of “native” proteins through the secretory pathway. Currently, ER-associated degradation (ERAD), which delivers misfolded proteins for degradation by the proteasome, is considered a major ERQC pathway, with autophagy as its backup. Until now, the role of autophagy, which shuttles cellular components for degradation in the lysosome through autophagosomes (APs), in ERQC was ill defined. Recently, the process of ER degradation induced by ER stress was defined as micro-ER-phagy, which does not require autophagic machinery and does not pass through APs. Here, we characterize the macro-ER-phagy pathway, which delivers excess membrane proteins for degradation in the lysosome, as a novel ERQC pathway. This pathway functions in the absence of cellular or ER stress and can be further induced by overexpression of a single integral-membrane protein. Unlike the micro-ER-phagy pathway, the marco-ER-phagy pathway requires core autophagy-specific proteins, Atgs, and Ypt/Rab GTPases. In addition, for the first time, the function of the only membrane core Atg, Atg9, was uncoupled from that of the other core Atgs. Whereas Atg9 plays a role in the assembly of ER-to-autophagy membranes (ERAM), other core Atgs and Ypt1 assemble the Atg-protein complex on ERAM to form the pre-autophagosomal structure.
Vyšlo v časopise:
A Role for Macro-ER-Phagy in ER Quality Control. PLoS Genet 11(7): e32767. doi:10.1371/journal.pgen.1005390
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.pgen.1005390
Souhrn
ER-quality control (ERQC) ensures delivery of “native” proteins through the secretory pathway. Currently, ER-associated degradation (ERAD), which delivers misfolded proteins for degradation by the proteasome, is considered a major ERQC pathway, with autophagy as its backup. Until now, the role of autophagy, which shuttles cellular components for degradation in the lysosome through autophagosomes (APs), in ERQC was ill defined. Recently, the process of ER degradation induced by ER stress was defined as micro-ER-phagy, which does not require autophagic machinery and does not pass through APs. Here, we characterize the macro-ER-phagy pathway, which delivers excess membrane proteins for degradation in the lysosome, as a novel ERQC pathway. This pathway functions in the absence of cellular or ER stress and can be further induced by overexpression of a single integral-membrane protein. Unlike the micro-ER-phagy pathway, the marco-ER-phagy pathway requires core autophagy-specific proteins, Atgs, and Ypt/Rab GTPases. In addition, for the first time, the function of the only membrane core Atg, Atg9, was uncoupled from that of the other core Atgs. Whereas Atg9 plays a role in the assembly of ER-to-autophagy membranes (ERAM), other core Atgs and Ypt1 assemble the Atg-protein complex on ERAM to form the pre-autophagosomal structure.
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Štítky
Genetika Reprodukčná medicínaČlánok vyšiel v časopise
PLOS Genetics
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