Physiological and pharmacological modulation of BAX

Adam Z. Spitz, Evripidis Gavathiotis

Research output: Contribution to journalReview articlepeer-review

1 Scopus citations

Abstract

Bcl-2-associated X protein (BAX) is a critical executioner of mitochondrial regulated cell death through its lethal activity of permeabilizing the mitochondrial outer membrane (MOM). While the physiological function of BAX ensures tissue homeostasis, dysregulation of BAX leads to aberrant cell death. Despite BAX being a promising therapeutic target for human diseases, historically the development of drugs has focused on antiapoptotic BCL-2 proteins, due to challenges in elucidating the mechanism of BAX activation and identifying druggable surfaces of BAX. Here, we discuss recent studies that have provided structure–function insights and identified regulatory surfaces that control BAX activation. Moreover, we emphasize the development of small molecule orthosteric, allosteric, and oligomerization modulators that provide novel opportunities for biological investigation and progress towards drugging BAX.

Original languageEnglish (US)
Pages (from-to)206-220
Number of pages15
JournalTrends in Pharmacological Sciences
Volume43
Issue number3
DOIs
StatePublished - Mar 2022

Keywords

  • BAX
  • BAX activators
  • BAX inhibitors
  • BCL-2 family
  • apoptosis
  • mitochondria

ASJC Scopus subject areas

  • Toxicology
  • Pharmacology

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