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Molecular cross-talk between the NRF2/KEAP1 signaling pathway, autophagy, and apoptosis

Tomasz M Stępkowski1, Marcin K Kruszewski

  • 1Institute of Nuclear Chemistry and Technology, Center for Radiobiology and Biological Dosimetry, 03-195 Warsaw, Poland. t.stepkowski@ichtj.waw.pl

Free Radical Biology & Medicine
|February 8, 2011
PubMed

Insights

The NRF2/KEAP1 pathway regulates cell defense against oxidative stress. This article hypothesizes how its interactants, like KEAP1, may link this pathway to apoptosis and autophagy, impacting diseases.

Area of Science:

  • Cellular Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Oxidative stress disrupts cellular thiol levels and redox balance, influencing signaling pathways like autophagy and apoptosis.
  • The NRF2/KEAP1 pathway is crucial for cellular defense against oxidative stress and maintaining redox homeostasis.
  • The precise relationship between NRF2/KEAP1 signaling and the regulation of apoptosis and autophagy remains unclear.

Purpose of the Study:

  • To explore the molecular mechanisms underlying the cross-talk between the NRF2/KEAP1 pathway, apoptosis, and autophagy.
  • To hypothesize how KEAP1 interactants mediate these cellular processes.
  • To discuss the implications for carcinogenesis and neurodegenerative diseases.

Main Methods:

  • This is a hypothesis article, presenting theoretical frameworks based on existing experimental evidence.
  • Discussion of molecular interactions and signaling pathway cross-talk.
  • Review of recent findings on KEAP1 binding partners and their roles.

Main Results:

  • KEAP1 interactants (PGAM5, prothymosin α, FAC1, p62) may provide a molecular basis for cross-talk between NRF2/KEAP1, apoptosis, and autophagy.
  • Hypothesized activation of ASK1 kinase by KEAP1-PGAM5 linking NRF2/KEAP1 to apoptosis.
  • Presented hypotheses for NRF2/KEAP1 and NF-κB cross-talk via p62 in autophagy.

Conclusions:

  • KEAP1 binding partners are proposed as key mediators in the interplay between oxidative stress response, apoptosis, and autophagy.
  • Understanding these interactions may offer insights into therapeutic strategies for diseases involving dysregulated apoptosis and autophagy.
  • The roles of KEAP1 interactants in apoptosis during carcinogenesis and neurodegeneration warrant further investigation.

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