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

We describe the role of reactive oxygen species as signaling molecules in starvation-induced autophagy

Ruth Scherz-Shouval; Elena Shvets; Ephraim Fass; Hagai Shorer; Lidor Gil; Zvulun Elazar


Scholarcy highlights

  • Autophagy is a major pathway for delivery of proteins and organelles to lysosomes/the vacuole, where they are degraded and recycled
  • To rule out the possibility that the oxidative signal associated with starvation is leading to programmed cell death, we tested the viability of cells grown under nutrient starvation conditions
  • Taken together with the finding that the oxidative signal appears minutes after induction of starvation, these results suggest that H2O2 serves as a signaling molecule in the autophagic pathway, and not as part of an oxidative stress leading to PCD
  • Many of the proteins involved in this process have been identified, the signal transduction pathway leading to activation of autophagy is not fully solved
  • We show that starvation triggers accumulation of reactive oxygen species, most probably H2O2, which is necessary for autophagosome formation and the resulting pathway of degradation
  • We found nearly 40% less of the lipidated form of GATE-16 in cells transfected with HsAtg4AC81S as compared with cells transfected with HsAtg4AWT
  • We identify a direct target for oxidation by H2O2—the protease Atg4
  • Redox regulation of Atg4 can provide rapid activation and inactivation of this protease, as part of the signaling pathway, leading to induction of the autophagic process

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