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  • The EMBO Journal (2007) 26, 1749 - 1760
  • doi:10.1038/sj.emboj.7601623

Published online: 8 March 2007

Reactive oxygen species are essential for autophagy and specifically regulate the activity of Atg4

Ruth Scherz-Shouval1, Elena Shvets1, Ephraim Fass1, Hagai Shorer1, Lidor Gil1 and Zvulun Elazar1

  1. Department of Biological Chemistry, The Weizmann Institute of Science, Rehovot, Israel

Correspondence to:

Zvulun Elazar, Department of Biological Chemistry, The Weizmann Institute of Science, Rehovot, 76100 Israel. Tel.: +972 8 9343682; Fax: +972 8 9344112; E-mail: bmzevi@wicc.weizmann.ac.il

Received 31 August 2006; Accepted 24 January 2007

Autophagy is a major catabolic pathway by which eukaryotic cells degrade and recycle macromolecules and organelles. This pathway is activated under environmental stress conditions, during development and in various pathological situations. In this study, we describe the role of reactive oxygen species (ROS) as signaling molecules in starvation-induced autophagy. We show that starvation stimulates formation of ROS, specifically H2O2. These oxidative conditions are essential for autophagy, as treatment with antioxidative agents abolished the formation of autophagosomes and the consequent degradation of proteins. Furthermore, we identify the cysteine protease HsAtg4 as a direct target for oxidation by H2O2, and specify a cysteine residue located near the HsAtg4 catalytic site as a critical for this regulation. Expression of this regulatory mutant prevented the formation of autophagosomes in cells, thus providing a molecular mechanism for redox regulation of the autophagic process.

  • Keywords:

    • Atg4,
    • autophagy,
    • GATE-16,
    • ROS
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