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Emerging lysosomal pathways for quality control at the endoplasmic reticulum
Author(s) -
De Leonibus Chiara,
Cinque Laura,
Settembre Carmine
Publication year - 2019
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1002/1873-3468.13571
Subject(s) - endoplasmic reticulum associated protein degradation , endoplasmic reticulum , microbiology and biotechnology , lysosome , protein folding , cytosol , biology , unfolded protein response , chemistry , biochemistry , enzyme
Protein misfolding occurring in the endoplasmic reticulum (ER) might eventually lead to aggregation and cellular distress, and is a primary pathogenic mechanism in multiple human disorders. Mammals have developed evolutionary‐conserved quality control mechanisms at the level of the ER. The best characterized is the ER‐associated degradation (ERAD) pathway, through which misfolded proteins translocate from the ER to the cytosol and are subsequently proteasomally degraded. However, increasing evidence indicates that additional quality control mechanisms apply for misfolded ER clients that are not eligible for ERAD. This review focuses on the alternative, ERAD‐independent, mechanisms of clearance of misfolded polypeptides from the ER. These processes, collectively referred to as ER‐to‐lysosome–associated degradation, involve ER‐phagy, microautophagy or vesicular transport. The identification of the underlying molecular mechanisms is particularly important for developing new therapeutic approaches for human diseases associated with protein aggregate formation.