FAD transport and FAD-dependent protein thiol oxidation in rat liver microsomes.
The transport of FAD and its effect on disulfide bond formation was investigated in rat liver microsomal vesicles. By measuring the intravesicular FAD-accessible space, we observed that FAD permeates across the microsomal membrane and accumulates in the lumen. Rapid filtration experiments also demonstrated the uptake and efflux of the compound, which could be inhibited by atractyloside and 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid. FAD entering the lumen promoted the oxidation of protein thiols and increased the intraluminal oxidation of glucose-6-phosphate. These findings support the notion that, similar to yeast, free FAD may have a decisive role in the mechanism of oxidative protein folding in the endoplasmic reticulum lumen of mammalian cells.
Varsányi
Marianne
M
Department of Medical Chemistry, Molecular Biology and Pathobiochemistry, Semmelweis University, 1444 Budapest, Hungary.
Szarka
András
A
Papp
Eszter
E
Makai
Dóra
D
Nardai
Gábor
G
Fulceri
Rosella
R
Csermely
Péter
P
Mandl
József
J
Benedetti
Angelo
A
Bánhegyi
Gábor
G
D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid / Q000494:pharmacology; D000818:Animals; D001278:Atractyloside / Q000494:pharmacology; D001692:Biological Transport; D003600:Cytosol / Q000378:metabolism; D004220:Disulfides; D004305:Dose-Response Relationship, Drug; D004721:Endoplasmic Reticulum / Q000378:metabolism; D005182:Flavin-Adenine Dinucleotide / Q000737:chemistry*; D007425:Intracellular Membranes / Q000378:metabolism; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism; D011485:Protein Binding; D051381:Rats; D017207:Rats, Sprague-Dawley; D013438:Sulfhydryl Compounds / Q000737:chemistry / Q000378:metabolism; D013997:Time Factors
D004220:Disulfides; D013438:Sulfhydryl Compounds; D005182:Flavin-Adenine Dinucleotide; D001278:Atractyloside; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid; D010100:Oxygen