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Updated: Jan 30, 2026

Exploring the Regulation of Lipid Droplet Catabolism through Lipophagy
Published on: January 31, 2025
Mechanistic insight into the regulation of SQSTM1/p62
Yi Zhang1, Su Ran Mun2, Juan F Linares3
1a Department of Pharmacology , University of Colorado School of Medicine , Aurora , CO , USA.
Abstract:
SQSTM1/p62 facilitates responses to various cellular stresses and has been implicated in human diseases. This protein functions as a major cytoplasmic signaling hub and has multiple binding partners, including arginylated (Nt-R) proteins that are recognized by the ZZ domain of SQSTM1/p62 (SQSTM1/p62ZZ). We have determined the molecular mechanism of Nt-R recognition using a combination of biochemical and NMR approaches and obtained the crystal structure of SQSTM1/p62ZZ in complex with Nt-R. We found that binding of SQSTM1/p62ZZ to Nt-R induces SQSTM1/p62 puncta formation and macroautophagy/autophagy and identified a regulatory linker (RL) region of SQSTM1/p62 that associates with SQSTM1/p62ZZ in vitro. Our findings suggest a mechanism for SQSTM1/p62 autoregulation that can be essential in mediating autophagy.
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