Transcription Factor Deformed Wings Is an Atg8a-Interacting Protein That Regulates Autophagy

Area of Science:

• Molecular Biology
• Cellular Biology
• Genetics

Background:

• Microtubule-associated protein 1 light chain 3 (LC3), also known as Atg8, is crucial for selective autophagy.
• While primarily cytoplasmic, LC3 proteins are also found in the nucleus, but their nuclear functions and import mechanisms are unclear.
• Selective autophagy relies on interactions between LC3/Atg8 and LIR/AIM motifs on cargo receptors.

Purpose of the Study:

• To investigate the nuclear interactions and functions of Atg8 family proteins.
• To identify novel nuclear proteins interacting with Atg8 in Drosophila.
• To elucidate the role of the Atg8-Deformed wings (Dwg) interaction in regulating autophagy.

Main Methods:

• Yeast two-hybrid screening to identify Atg8a-interacting proteins in Drosophila.
• Creation and analysis of Drosophila mutants with a disrupted Dwg LIR motif (Y129A/I132A).
• Assessment of autophagy levels, oxidative stress resistance, and starvation resistance in mutant flies.

Main Results:

• Identified Deformed wings (Dwg), a transcription factor, as a novel Atg8a-interacting protein in Drosophila.
• Confirmed the interaction is dependent on the LIR motif within Dwg.
• Dwg LIR mutant flies exhibited significantly elevated autophagy and enhanced resistance to oxidative stress and starvation.

Conclusions:

• The interaction between Atg8a and Dwg plays a critical role in regulating autophagy.
• This interaction is important for maintaining cellular homeostasis under stress conditions.
• Provides novel insights into the transcriptional regulation of autophagy via nuclear LC3/Atg8 interactions in Drosophila.