Antibacterial autophagy occurs at PI(3)P-enriched domains of the endoplasmic reticulum and requires Rab1 GTPase.
Autophagy mediates the degradation of cytoplasmic components in eukaryotic cells and plays a key role in immunity. The mechanism of autophagosome formation is not clear. Here we examined two potential membrane sources for antibacterial autophagy: the ER and mitochondria. DFCP1, a marker of specialized ER domains known as 'omegasomes,' associated with Salmonella-containing autophagosomes via its PtdIns(3)P and ER-binding domains, while a mitochondrial marker (cytochrome b5-GFP) did not. Rab1 also localized to autophagosomes, and its activity was required for autophagosome formation, clearance of protein aggregates and peroxisomes, and autophagy of Salmonella. Overexpression of Rab1 enhanced antibacterial autophagy. The role of Rab1 in antibacterial autophagy was independent of its role in ER-to-Golgi transport. Our data suggest that antibacterial autophagy occurs at omegasomes and reveal that the Rab1 GTPase plays a crucial role in mammalian autophagy.
Huang
Ju
J
Cell Biology Program, Hospital for Sick Children, Toronto, ON, Canada.
Birmingham
Cheryl L
CL
Shahnazari
Shahab
S
Shiu
Jessica
J
Zheng
Yiyu T
YT
Smith
Adam C
AC
Campellone
Kenneth G
KG
Heo
Won Do
WD
Gruenheid
Samantha
S
Meyer
Tobias
T
Welch
Matthew D
MD
Ktistakis
Nicholas T
NT
Kim
Peter Kijun
PK
Klionsky
Daniel J
DJ
Brumell
John H
JH
D000818:Animals; D001343:Autophagy; D002352:Carrier Proteins / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000201:enzymology*; D006056:Golgi Apparatus / Q000187:drug effects / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D007425:Intracellular Membranes / Q000187:drug effects / Q000201:enzymology*; D051379:Mice; D020675:Peroxisomes / Q000187:drug effects / Q000378:metabolism; D010588:Phagosomes / Q000382:microbiology; D018129:Phosphatidylinositol Phosphates / Q000378:metabolism*; D020836:Protein Structure, Quaternary; D021381:Protein Transport / Q000187:drug effects; D012486:Salmonella typhimurium / Q000276:immunology*; D020123:Sirolimus / Q000494:pharmacology; D057149:Ubiquitinated Proteins / Q000737:chemistry; D020761:rab1 GTP-Binding Proteins / Q000378:metabolism*
D002352:Carrier Proteins; D018129:Phosphatidylinositol Phosphates; D057149:Ubiquitinated Proteins; C426003:ZFYVE1 protein, human; C055525:phosphatidylinositol 3-phosphate; D020761:rab1 GTP-Binding Proteins; D020123:Sirolimus