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Author Spotlight: Imaging ATG9A, a Multi-Spanning Membrane Protein
Published on: June 16, 2023
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Dimerization-dependent membrane tethering by Atg23 is essential for yeast autophagy
Wayne D Hawkins1, Kelsie A Leary2, Devika Andhare2
1Life Sciences Institute, University of Michigan, Ann Arbor, MI 48109, USA; Department of Molecular, Cellular and Developmental Biology, University of Michigan, Ann Arbor, MI 48109, USA.
Cell Reports
|April 20, 2022
Summary
Atg23 forms a homodimer crucial for macroautophagy. This dimer, with its rod-like structure and membrane interactions, is essential for cellular health and efficient cargo degradation.
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- Macroautophagy is vital for eukaryotic cellular health, involving cargo engulfment and degradation.
- Atg23's function in macroautophagy is poorly understood due to limited biochemical and structural data.
Purpose of the Study:
- To elucidate the structure and function of Atg23 in macroautophagy.
- To investigate the role of Atg23 dimerization in its cellular activities.
Main Methods:
- In vitro and in vivo biochemical assays.
- Small-angle X-ray scattering (SAXS) for structural analysis.
- Site-directed mutagenesis to probe protein function.
Main Results:
- Atg23 primarily exists as a homodimer, stabilized by an amphipathic helix.
- SAXS revealed an extended, rod-like structure of approximately 320 Å for Atg23.
- Atg23 directly interacts with membranes via electrostatic forces, mediating vesicle tethering.
- Mutating the amphipathic helix disrupted dimerization, impairing localization, tethering, Atg9 binding, and autophagic efficiency.
Conclusions:
- Atg23 dimerization is critical for its function in macroautophagy.
- The structural and membrane-binding properties of Atg23 are essential for autophagosome formation and cellular homeostasis.
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