Endoplasmic Reticulum Transport of Glutathione by Sec61 Is Regulated by Ero1 and Bip.
Mol Cell
; 67(6): 962-973.e5, 2017 Sep 21.
Article
in En
| MEDLINE
| ID: mdl-28918898
ABSTRACT
In the endoplasmic reticulum (ER), Ero1 catalyzes disulfide bond formation and promotes glutathione (GSH) oxidation to GSSG. Since GSSG cannot be reduced in the ER, maintenance of the ER glutathione redox state and levels likely depends on ER glutathione import and GSSG export. We used quantitative GSH and GSSG biosensors to monitor glutathione import into the ER of yeast cells. We found that glutathione enters the ER by facilitated diffusion through the Sec61 protein-conducting channel, while oxidized Bip (Kar2) inhibits transport. Increased ER glutathione import triggers H2O2-dependent Bip oxidation through Ero1 reductive activation, which inhibits glutathione import in a negative regulatory loop. During ER stress, transport is activated by UPR-dependent Ero1 induction, and cytosolic glutathione levels increase. Thus, the ER redox poise is tuned by reciprocal control of glutathione import and Ero1 activation. The ER protein-conducting channel is permeable to small molecules, provided the driving force of a concentration gradient.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Saccharomyces cerevisiae
/
Fungal Proteins
/
Glycoproteins
/
HSP70 Heat-Shock Proteins
/
Saccharomyces cerevisiae Proteins
/
Endoplasmic Reticulum
/
Oxidoreductases Acting on Sulfur Group Donors
/
SEC Translocation Channels
/
Glutathione
Language:
En
Journal:
Mol Cell
Journal subject:
BIOLOGIA MOLECULAR
Year:
2017
Document type:
Article
Affiliation country:
France