NBR1: The archetypal selective autophagy receptor

Area of Science:

• Cell Biology
• Molecular Biology
• Evolutionary Biology

Background:

• NBR1 and p62/SQSTM1 are autophagy receptors involved in selective autophagy.
• p62 is extensively studied, while NBR1 research is less prevalent.
• Evolutionary analysis indicates NBR1 predates p62, existing since the Last Eukaryotic Common Ancestor (LECA).

Purpose of the Study:

• To explore the evolutionary history and functional significance of the autophagy receptor NBR1.
• To investigate the comparative roles of NBR1 and p62 in selective autophagy.
• To elucidate NBR1's involvement in protein aggregate degradation and human diseases.

Main Methods:

• Evolutionary and comparative genomic analyses.
• Mechanistic studies on NBR1 function in selective autophagy.
• Analysis of NBR1's role in proteinopathies and cancer.

Main Results:

• NBR1 homologs are found in yeast (Atg19, Atg34), predating p62's appearance in Metazoa.
• NBR1 is the primary autophagy receptor in plants, which lack p62.
• NBR1 and p62 collaborate in mammalian aggrephagy, with NBR1 recognizing diverse substrates.

Conclusions:

• NBR1 represents an evolutionarily conserved and functionally significant autophagy receptor.
• NBR1 plays crucial roles in selective autophagy, cargo recognition, and disease pathogenesis.
• Further research into NBR1 is warranted given its emerging roles in human health and disease.