A nuclear role for Atg8-family proteins

Area of Science:

• Cellular Biology
• Molecular Biology
• Genetics

Background:

• The nuclear localization of microtubule-associated protein 1A/1B-light chain 3 (LC3) is increasingly recognized, yet the underlying mechanisms and functional significance remain unclear.
• Autophagy, a fundamental cellular process, is tightly regulated at multiple levels, including transcriptional control.

Purpose of the Study:

• To elucidate the mechanisms governing the nuclear targeting and function of the LC3 homolog, Atg8a, in *Drosophila*.
• To investigate the role of Atg8a in the transcriptional regulation of autophagy genes.

Main Methods:

• Co-immunoprecipitation assays to identify protein-protein interactions.
• Analysis of protein acetylation status using Western blotting.
• Luciferase reporter assays to assess transcriptional activity.
• Genetic manipulation in *Drosophila* to study gene function.

Main Results:

• The *Drosophila* LC3 homolog, Atg8a, interacts with the transcription factor seq (sequoia) via its LIR motif, negatively regulating autophagy gene transcription.
• Atg8a also interacts with the nuclear acetyltransferase YL-1 and deacetylase Sirt2, indicating its acetylation status is dynamically regulated.
• Acetylation of Atg8a by YL-1 and Sirt2 modulates the Atg8a-seq interaction, thereby controlling autophagy gene induction and the overall autophagy process.

Conclusions:

• This study uncovers a novel nuclear role for Atg8a in the transcriptional regulation of autophagy.
• The findings highlight a mechanism where Atg8a's nuclear function is controlled by its acetylation status, linking post-translational modification to gene expression and cellular homeostasis.