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Identification of glucose-6-phosphate transporter as a key regulator functioning at the autophagy initiation step

Hye-Hyun Ahn1, Yumin Oh2, Huikyong Lee3

  • 1Global Research Laboratory, School of Biological Science, Seoul National University, Gwanak-gu, Seoul, Republic of Korea; Interdisciplinary Graduate Program in Genetic Engineering, Seoul National University, Gwanak-gu, Seoul, Republic of Korea.

FEBS Letters
|May 19, 2015
PubMed

Insights

Researchers identified G6PT as a novel autophagy activator. G6PT enhances the ULK1-ATG9 interaction and stimulates autophagy by negatively regulating mTORC1 activity, functioning upstream in the pathway.

Area of Science:

  • Cellular Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Autophagy is a crucial cellular catabolic process involving autophagosome formation and lysosomal degradation.
  • The precise initiation mechanisms of autophagy, particularly upstream regulators of ULK1, remain incompletely understood.

Purpose of the Study:

  • To identify novel regulators of autophagy acting upstream of ULK1.
  • To investigate the role of G6PT in the autophagy pathway.

Main Methods:

  • Development of a cell-based screening assay utilizing bimolecular fluorescence complementation (BiFC).
  • Performing a gain-of-function screen to identify autophagy activators.
  • Assessing the effect of G6PT on the ULK1-ATG9 interaction and autophagic flux.
  • Evaluating G6PT's impact on mTORC1 activity.

Main Results:

  • G6PT was identified as an autophagy activator through a gain-of-function screen.
  • G6PT enhanced the interaction between ULK1 and ATG9.
  • G6PT increased autophagic flux independently of its known transport activity.
  • G6PT was found to negatively regulate mTORC1 activity.

Conclusions:

  • G6PT acts as an upstream activator of autophagy.
  • G6PT stimulates autophagy by promoting the ULK1-ATG9 interaction and inhibiting mTORC1 signaling.
  • These findings reveal a novel regulatory mechanism in autophagy initiation.
Keywords:
ATG9Autophagy modulatorG6PTScreeningULK1

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