Depletion of Luminal Pyridine Nucleotides in the Endoplasmic Reticulum Activates Autophagy with the Involvement of mTOR Pathway. (17th November 2013)

• Record Type: Journal Article
• Authors: Kapuy, Orsolya; Bánhegyi, Gábor
• Other Names: Angeloni Cristina Academic Editor.
• Is Part Of: BioMed research international. Volume 2013(2013)
• Publication Date: 2013-11-17
• Subjects: Medicine -- Periodicals; Biology -- Periodicals; Biotechnology -- Periodicals; Life sciences -- Periodicals; 610.5
• DOI: 10.1155/2013/942431
• Languages: English
• ISSNs: 2314-6133

Abstract

Abstract : It has been recently shown that redox imbalance of luminal pyridine nucleotides in the endoplasmic reticulum (ER) together with oxidative stress results in the activation of autophagy. In the present study we demonstrated that decrease of luminal NADPH/NADP + ratio alone by metyrapone was sufficient to promote the mechanism of "self-eating" detected by the activation of LC3. Depletion of luminal NADPH had also significant effect on the key proteins of mTOR pathway, which got inactivated by dephosphorylation. These findings were also confirmed by silencing the proteins (glucose-6-phosphate transporter and hexose-6-phosphate dehydrogenase) responsible for NADPH generation in the ER lumen. However, silencing the key components and addition of metyrapone had different effects on downstream substrates 4EBP1 and p70S6K of mTOR. The applied treatments did not compromise the viability of the cells. Our data suggest that ER stress caused by luminal NADPH depletion activates a pro-survival autophagic mechanism firmly coupled to the activation of mTOR pathway.