Rapid activation of p62 body-mediated autophagy in human cells under hyperosmotic stress

Abstract

The autophagy receptor p62 is degraded via autophagy under hyperosmotic stress, but whether this involves the formation of biomolecular condensates (p62 bodies) remains unclear. Using human cells, we found that p62 bodies formed within 1 minute of hyperosmotic stress, and increased with stress severity. They formed faster and under milder stress than stress granules, a classic condensate, and exhibited liquid-like properties. Unlike stress granules, p62 bodies frequently colocalized with LC3 and WIPI-2, and were degraded via autophagy. Correlative light and electron microscopy revealed that these p62 bodies were more compact than stress granules and were often associated with the autophagic isolation membrane. Autophagy receptors NBR1 and TAX1BP1, but not OPTN1 or NDP52, behaved similarly to p62, and p62 bodies preferentially contained K63-linked ubiquitin chains. p62 body formation was also observed in human epithelial organoids in association with WIPI-2. Collectively, these results indicate that p62 bodies function as a platform of degradation under hyperosmotic stress.