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TMEM 41B is a novel regulator of autophagy and lipid mobilization
Author(s) -
Moretti Francesca,
Bergman Phil,
Dodgson Stacie,
Marcellin David,
Claerr Isabelle,
Goodwin Jonathan M,
DeJesus Rowena,
Kang Zhao,
Antczak Christophe,
Begue Damien,
Bonenfant Debora,
Graff Alexandra,
Genoud Christel,
ReeceHoyes John S,
Russ Carsten,
Yang Zinger,
Hoffman Gregory R,
Mueller Matthias,
Murphy Leon O,
Xavier Ramnik J,
Nyfeler Beat
Publication year - 2018
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.15252/embr.201845889
Subject(s) - autophagy , microbiology and biotechnology , autophagosome , endoplasmic reticulum , biogenesis , biology , regulator , atg8 , phagosome , organelle biogenesis , signal transducing adaptor protein , lipid droplet , unfolded protein response , endocytic cycle , bag3 , receptor , signal transduction , intracellular , biochemistry , endocytosis , apoptosis , gene
Autophagy maintains cellular homeostasis by targeting damaged organelles, pathogens, or misfolded protein aggregates for lysosomal degradation. The autophagic process is initiated by the formation of autophagosomes, which can selectively enclose cargo via autophagy cargo receptors. A machinery of well‐characterized autophagy‐related proteins orchestrates the biogenesis of autophagosomes; however, the origin of the required membranes is incompletely understood. Here, we have applied sensitized pooled CRISPR screens and identify the uncharacterized transmembrane protein TMEM 41B as a novel regulator of autophagy. In the absence of TMEM 41B, autophagosome biogenesis is stalled, LC 3 accumulates at WIPI 2‐ and DFCP 1‐positive isolation membranes, and lysosomal flux of autophagy cargo receptors and intracellular bacteria is impaired. In addition to defective autophagy, TMEM 41B knockout cells display significantly enlarged lipid droplets and reduced mobilization and β‐oxidation of fatty acids. Immunostaining and interaction proteomics data suggest that TMEM 41B localizes to the endoplasmic reticulum ( ER ). Taken together, we propose that TMEM 41B is a novel ER ‐localized regulator of autophagosome biogenesis and lipid mobilization.