Autophagy cargo recognition and clearance are essential for intracellular protein quality control. SQSTM1/p62 sequesters intracellular aberrant proteins and mediates cargo delivery for their selective autophagic degradation. The formation of p62 non-membrane-bound liquid compartments is critical for its function as a cargo receptor. The regulation of p62 phase separation/condensation has yet been poorly characterised. Using an unbiased yeast two-hybrid screening and complementary approaches, we found that DAXX physically interacts with p62. Cytoplasmic DAXX promotes p62 puncta formation. We further elucidate that DAXX drives p62 liquid phase condensation by inducing p62 oligomerisation. This effect promotes p62 recruitment of Keap1 and subsequent Nrf2-mediated stress response. The present study suggests a mechanism of p62 phase condensation by a protein interaction, and indicates that DAXX regulates redox homoeostasis, providing a mechanistic insight into the prosurvival function of DAXX.
[1]Univ Plymouth, Fac Med & Dent, Peninsula Med Sch, Inst Translat & Stratified Med, Res Way, Plymouth PL6 8BU, Devon, England;
[2]Fudan Univ, Sch Life Sci, State Key Lab Med Neurobiol, Shanghai 200438, Peoples R China;
[3]Univ Plymouth, Fac Med & Dent, Peninsula Dent Sch, 16 Res Way, Plymouth PL6 8BU, Devon, England;
[4]Thomas Jefferson Univ, Dept Microbiol & Immunol, Philadelphia, PA 19107 USA
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