Cysteine and glutathione secretion in response to protein disulfide bond formation in the ER.
Protein folding in the endoplasmic reticulum (ER) often involves the formation of disulfide bonds. The oxidizing conditions required within this organelle were shown to be maintained through the release of small thiols, mainly cysteine and glutathione. Thiol secretion was stimulated when proteins rich in disulfide bonds were translocated into the ER, and secretion was prevented by the inhibition of protein synthesis. Endogenously generated cysteine and glutathione counteracted thiol-mediated retention in the ER and altered the extracellular redox. The secretion of thiols might link disulfide bond formation in the ER to intra- and intercellular redox signaling.
Carelli
S
S
DIBIT, Istituto Scientifico San Raffaele, Milano, Italy.
Ceriotti
A
A
Cabibbo
A
A
Fassina
G
G
Ruvo
M
M
Sitia
R
R
D000818:Animals; D001578:Benzopyrans / Q000378:metabolism; D020126:Brefeldin A; D003513:Cycloheximide / Q000494:pharmacology; D003517:Cyclopentanes / Q000494:pharmacology; D003545:Cysteine / Q000378:metabolism*; D003553:Cystine / Q000378:metabolism; D004220:Disulfides / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D005089:Exocytosis; D005978:Glutathione / Q000031:analogs & derivatives / Q000378:metabolism*; D019803:Glutathione Disulfide; D006056:Golgi Apparatus / Q000378:metabolism; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000096:biosynthesis; D007075:Immunoglobulin M / Q000096:biosynthesis; D007146:Immunoglobulin lambda-Chains / Q000378:metabolism; D009865:Oocytes; D010084:Oxidation-Reduction; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D011506:Proteins / Q000378:metabolism*; D013696:Temperature; D014407:Tumor Cells, Cultured; D014982:Xenopus laevis
D001578:Benzopyrans; D003517:Cyclopentanes; D004220:Disulfides; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007075:Immunoglobulin M; D007146:Immunoglobulin lambda-Chains; D011500:Protein Synthesis Inhibitors; D011506:Proteins; D020126:Brefeldin A; D003553:Cystine; D003513:Cycloheximide; D005978:Glutathione; D003545:Cysteine; D019803:Glutathione Disulfide