Nuclear-accumulated SQSTM1/p62-based ALIS act as microdomains sensing cellular stresses and triggering oxidative stress-induced parthanatos

Takuya Noguchi, Midori Suzuki, Natsumi Mutoh, Yusuke Hirata, Mei Tsuchida, Sayoko Miyagawa, Gi Wook Hwang, Junken Aoki, Atsushi Matsuzawa

Research output: Contribution to journalArticlepeer-review

15 Citations (Scopus)

Abstract

Aggresome-like induced structures (ALIS) have been described as ubiquitinated protein-containing aggresomes transiently formed in response to various stresses. In this study, we provide evidence that ALIS composed of SQSTM1/p62 act as a key determinant of oxidative stress-induced parthanatos, which is newly discovered and distinct from regular programmed cell death. Interestingly, we first found that chemical stresses induced by particular chemical drugs, such as several cephalosporin antibiotics, cause oxidative stress-mediated parthanatos, accompanied by the ALIS formation. Blocking the ALIS formation potently suppressed the parthanatos, and p62 knockout cells exhibited the attenuated ALIS formation and high resistance to parthanatos. Moreover, we also found that the redox-sensing activity of p62 is required for nuclear accumulation of the p62-based ALIS, resulting in the induction of parthanatos. Together, our results demonstrate unexpected functions of p62 and ALIS as cell death mediators sensing oxidative stress, and thus uncover a novel mechanism whereby p62 mediates parthanatos.

Original languageEnglish
Article number1193
JournalCell Death and Disease
Volume9
Issue number12
DOIs
Publication statusPublished - 2018 Dec 1

ASJC Scopus subject areas

  • Immunology
  • Cellular and Molecular Neuroscience
  • Cell Biology
  • Cancer Research

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