Mec1-mediated Atg9 phosphorylation regulates the PAS recruitment of Atg9 vesicles upon energy stress

Related Experiment Video

Updated: May 29, 2025

Author Spotlight: Imaging ATG9A, a Multi-Spanning Membrane Protein
07:20

Author Spotlight: Imaging ATG9A, a Multi-Spanning Membrane Protein

Published on: June 16, 2023

2.0K

Siyu Fan1, Shuling Dong2, Weijing Yao1

  • 1Department of Biochemistry and Department of Hepatobiliary and Pancreatic Surgery of the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310058, China.

Proceedings of the National Academy of Sciences of the United States of America
|February 6, 2025
PubMed

Insights

The kinase activity of Mec1 is crucial for glucose starvation-induced autophagy and DNA damage response. Mec1 phosphorylates Atg9, regulating Atg9 vesicle recruitment to the phagophore assembly site (PAS).

Area of Science:

  • Cellular Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Mec1 is vital for DNA damage response and autophagy.
  • Mec1 regulates autophagy via Atg13 binding, but its kinase role in autophagy is unknown.

Purpose of the Study:

  • To investigate the role of Mec1's kinase activity in glucose starvation-induced autophagy.
  • To elucidate the mechanism by which Mec1 regulates autophagy.

Main Methods:

  • Yeast genetics and molecular biology techniques.
  • Phosphorylation site analysis and protein-protein interaction studies.

Main Results:

  • Mec1 kinase activity is essential for autophagy induction during glucose starvation.
  • Atg9 is a direct phosphorylation substrate of Mec1 at specific sites (S35, T203, T243).
  • Phosphorylation of Atg9 by Mec1 is required for Atg9 vesicle recruitment to the phagophore assembly site (PAS) in both starvation and DNA damage conditions.

Conclusions:

  • Mec1's kinase activity regulates Atg9 vesicle recruitment to the PAS via Atg9 phosphorylation.
  • This mechanism is critical for autophagy during energy stress and DNA damage.
  • Mec1-Atg13 interaction is necessary for Mec1 to phosphorylate Atg9.
Keywords:
Atg9DNA damage–induced autophagyMec1Saccharomyces cerevisiaeglucose starvation–induced autophagy

More Related Videos

Time-Lapse Video Microscopy for Assessment of EYFP-Parkin Aggregation as a Marker for Cellular Mitophagy09:29

Time-Lapse Video Microscopy for Assessment of EYFP-Parkin Aggregation as a Marker for Cellular Mitophagy

Published on: May 4, 2016

7.1K
Study of Protein-protein Interactions in Autophagy Research14:08

Study of Protein-protein Interactions in Autophagy Research

Published on: September 9, 2017

9.1K

Related Concept Videos

Translocation of Proteins into the Mitochondria01:19

Translocation of Proteins into the Mitochondria

Mitochondrial precursors are translocated to the internal subcompartments via independent mechanisms involving distinct protein machineries called translocases.
Sorting of outer membrane proteins:
Mitochondrial outer membrane proteins are of two types: the transmembrane, beta-barrel porins, and the membrane-anchored, alpha-helical proteins. Beta-barrel porin precursors are translocated by the TOM complex and inserted into the outer mitochondrial membrane by the SAM complex. In contrast,...
3.0K
Energy to Drive Translocation01:37

Energy to Drive Translocation

Mitochondrial protein import is powered by two distinct energy sources: ATP hydrolysis and electrochemical potential across the inner membrane. Newly synthesized precursors are bound by cytosolic chaperones of the Hsp70 family, which guide them to the import receptors on the mitochondrial surface. Utilizing the energy of ATP hydrolysis, Hsp70 chaperones transfer these precursors to the TOM receptors on the mitochondrial outer membrane.
Generally, polypeptides are unfolded by two distinct...
2.0K
Export of Misfolded Proteins out of the ER01:32

Export of Misfolded Proteins out of the ER

After folding, the ER assesses the quality of secretory and membrane proteins. The correctly folded proteins are cleared by the calnexin cycle for transport to their final destination, while misfolded proteins are held back in the ER lumen. The ER chaperones attempt to unfold and refold the misfolded proteins but sometimes fail to achieve the correct native conformation. Such terminally misfolded proteins are then exported to the cytosol by ER-associated degradation or ERAD pathway for...
3.5K
Coat Assembly and GTPases01:33

Coat Assembly and GTPases

Vesicles incorporate different coat protein subunits in different cell locations, which changes the properties of the coat, such as the shape and geometry of the transport vesicles. Thus, vesicle coat proteins also play a significant role in cargo selection.
Coat assembly depends on the local availability of phosphatidylinositol phosphates or PIPs and GTP-binding proteins. Adaptor proteins, which link the coat proteins to the membrane, bind to these PIPs and play a crucial role in controlling...
3.5K
The Unfolded Protein Response01:37

The Unfolded Protein Response

The ER is the hub of protein synthesis in a cell. It has robust systems to quality control protein folding and also for degradation of terminally misfolded proteins. Under normal conditions, a small proportion of misfolded proteins that cannot be salvaged need to be transported to the cytoplasm by the ER-associated degradation or ERAD pathways. However, if the ERAD cannot handle the misfolded proteins, the cell activates the unfolded protein response or UPR to adjust the protein folding...
4.4K
Autophagy01:27

Autophagy

Autophagy is a self-digesting process by which a cell protects itself from threats both within and outside the cell, ranging from abnormal proteins to invading bacteria. In this process, obsolete components of the cell and invading microbes are degraded by hydrolytic enzymes active in an acidic environment of the lysosomal lumen.
An autophagic pathway consists of a series of signaling events activated in response to diverse stress and physiological conditions such as food deprivation,...
4.1K