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Metabolic-stress-induced rearrangement of the 14-3-3ζ interactome promotes autophagy via a ULK1- and AMPK-regulated 14-3-3ζ interaction with phosphorylated Atg9.

Publication ,  Journal Article
Weerasekara, VK; Panek, DJ; Broadbent, DG; Mortenson, JB; Mathis, AD; Logan, GN; Prince, JT; Thomson, DM; Thompson, JW; Andersen, JL
Published in: Mol Cell Biol
December 2014

14-3-3ζ promotes cell survival via dynamic interactions with a vast network of binding partners, many of which are involved in stress regulation. We show here that hypoxia (low glucose and oxygen) triggers a rearrangement of the 14-3-3ζ interactome to favor an interaction with the core autophagy regulator Atg9A. Our data suggest that the localization of mammalian Atg9A to autophagosomes requires phosphorylation on the C terminus of Atg9A at S761, which creates a 14-3-3ζ docking site. Under basal conditions, this phosphorylation is maintained at a low level and is dependent on both ULK1 and AMPK. However, upon induction of hypoxic stress, activated AMPK bypasses the requirement for ULK1 and mediates S761 phosphorylation directly, resulting in an increase in 14-3-3ζ interactions, recruitment of Atg9A to LC3-positive autophagosomes, and enhanced autophagosome production. These data suggest a novel mechanism whereby the level of autophagy induction can be modulated by AMPK/ULK1-mediated phosphorylation of mammalian Atg9A.

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Published In

Mol Cell Biol

DOI

EISSN

1098-5549

Publication Date

December 2014

Volume

34

Issue

24

Start / End Page

4379 / 4388

Location

United States

Related Subject Headings

  • Vesicular Transport Proteins
  • Stress, Physiological
  • Serine
  • Protein Serine-Threonine Kinases
  • Phosphorylation
  • Phagosomes
  • Membrane Proteins
  • Intracellular Signaling Peptides and Proteins
  • Humans
  • Hela Cells
 

Citation

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Weerasekara, V. K., Panek, D. J., Broadbent, D. G., Mortenson, J. B., Mathis, A. D., Logan, G. N., … Andersen, J. L. (2014). Metabolic-stress-induced rearrangement of the 14-3-3ζ interactome promotes autophagy via a ULK1- and AMPK-regulated 14-3-3ζ interaction with phosphorylated Atg9. Mol Cell Biol, 34(24), 4379–4388. https://doi.org/10.1128/MCB.00740-14
Weerasekara, Vajira K., David J. Panek, David G. Broadbent, Jeffrey B. Mortenson, Andrew D. Mathis, Gideon N. Logan, John T. Prince, David M. Thomson, J Will Thompson, and Joshua L. Andersen. “Metabolic-stress-induced rearrangement of the 14-3-3ζ interactome promotes autophagy via a ULK1- and AMPK-regulated 14-3-3ζ interaction with phosphorylated Atg9.Mol Cell Biol 34, no. 24 (December 2014): 4379–88. https://doi.org/10.1128/MCB.00740-14.
Weerasekara VK, Panek DJ, Broadbent DG, Mortenson JB, Mathis AD, Logan GN, et al. Metabolic-stress-induced rearrangement of the 14-3-3ζ interactome promotes autophagy via a ULK1- and AMPK-regulated 14-3-3ζ interaction with phosphorylated Atg9. Mol Cell Biol. 2014 Dec;34(24):4379–88.
Weerasekara, Vajira K., et al. “Metabolic-stress-induced rearrangement of the 14-3-3ζ interactome promotes autophagy via a ULK1- and AMPK-regulated 14-3-3ζ interaction with phosphorylated Atg9.Mol Cell Biol, vol. 34, no. 24, Dec. 2014, pp. 4379–88. Pubmed, doi:10.1128/MCB.00740-14.
Weerasekara VK, Panek DJ, Broadbent DG, Mortenson JB, Mathis AD, Logan GN, Prince JT, Thomson DM, Thompson JW, Andersen JL. Metabolic-stress-induced rearrangement of the 14-3-3ζ interactome promotes autophagy via a ULK1- and AMPK-regulated 14-3-3ζ interaction with phosphorylated Atg9. Mol Cell Biol. 2014 Dec;34(24):4379–4388.

Published In

Mol Cell Biol

DOI

EISSN

1098-5549

Publication Date

December 2014

Volume

34

Issue

24

Start / End Page

4379 / 4388

Location

United States

Related Subject Headings

  • Vesicular Transport Proteins
  • Stress, Physiological
  • Serine
  • Protein Serine-Threonine Kinases
  • Phosphorylation
  • Phagosomes
  • Membrane Proteins
  • Intracellular Signaling Peptides and Proteins
  • Humans
  • Hela Cells