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Ribose 5-phosphate isomerase inhibits LC3 processing and basal autophagy

Heintze, J; Costa, JR; Weber, M; Ketteler, R; (2016) Ribose 5-phosphate isomerase inhibits LC3 processing and basal autophagy. Cellular Signalling , 28 (9) pp. 1380-1388. 10.1016/j.cellsig.2016.06.015. Green open access

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Abstract

Autophagy and cellular metabolism are tightly linked processes, but how individual metabolic enzymes regulate the process of autophagy is not well understood. This study implicates ribose-5-phosphate isomerase (RPIA), a key regulator of the pentose phosphate pathway, in the control of autophagy. We used a dual gene deletion strategy, combining shRNA-mediated knockdown studies with CRISPR/Cas9 genome editing. Knockdown of RPIA by shRNA or genomic deletion by CRISPR/Cas9 genome editing, results in an increase of ATG4B-mediated LC3 processing and in the appearance of LC3-positive autophagosomes in cells. Increased LC3 processing upon knockdown of RPIA can be reversed by treatment with the antioxidant N-acetyl cysteine. The results are consistent with a model in which RPIA suppresses autophagy and LC3 processing by modulation of redox signaling.

Type: Article
Title: Ribose 5-phosphate isomerase inhibits LC3 processing and basal autophagy
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.cellsig.2016.06.015
Publisher version: http://dx.doi.org/10.1016/j.cellsig.2016.06.015
Language: English
Additional information: © 2016 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
Keywords: Autophagy, CRISPR, Cas9, Pentose phosphate pathway, RPIA, shRNA
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Lab for Molecular Cell Bio MRC-UCL
URI: https://discovery-pp.ucl.ac.uk/id/eprint/1502406
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